To see the other types of publications on this topic, follow the link: Epithelial mesenchyme transition.
Dissertations / Theses on the topic 'Epithelial mesenchyme transition'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'Epithelial mesenchyme transition.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Teague, Warwick J. "Mesenchyme-to-epithelial transition in pancreatic organogenesis." Thesis, University of Oxford, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.670115.
Full text
2
Cheung, Pak-yan. "Esophageal carcinogenesis : immortalization, transformation and epithelial-mesenchymal transition /." Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B41290379.
Full text
3
Cheung, Pak-yan, and 張柏欣. "Esophageal carcinogenesis: immortalization, transformation and epithelial-mesenchymal transition." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B41290379.
Full text
4
Han, ShuYi. "Histone variant H2A.Z : a master regulator of epithelial-to-mesenchymal transition." Phd thesis, Canberra, ACT : The Australian National University, 2014. http://hdl.handle.net/1885/151759.
Full text
5
Robertson, Stuart. "A study of the role of splenic mesenchyme-to-epithelial transition in islet neogenesis." Thesis, University of Edinburgh, 2010. http://hdl.handle.net/1842/29339.
Full textAbstract:
Type 1 Diabetes Mellitus (T1DM) affects millions of children worldwide and is increasing in prevalence. Exogenous insulin therapy is currently the mainstay of treatment but is unable to prevent the chronic complications of this disease. Islet transplantation is a successful, minimally-invasive, potentially curable alternative treatment, which has restored physiological euglycaemia in up to 85% of recipients in recent clinical trials. However, worldwide human donor islet shortages limit the wider application of this treatment. Pluripotent cells may provide alternative islet sources to overcome this shortage. The human spleen may be one such source and is an excellent candidate tissue for further investigation. The main aims of this thesis were to investigate whether the developing spleen could differentiate into insulin-producing cells and to investigate the molecular mechanisms behind this. Using an avian model of pancreatic development, I characterise normal avian foregut expression of the splenic mesenchymal transcription factor Tlx-1 between E4-E11 of development and report an optimised in situ hybridisation protocol for this. I use a chick-quail chimaera model of pancreatic organogenesis to show that the developing avian spleen is able to differentiate into insulin-producing cells in vitro through islet Mesenchyme-to-Epithelial Transition (iMET). 1 show evidence that, when recombined with differentiating pancreatic epithelium, splenic mesenchyme is reprogrammed to express the pancreatic islet genes Pdx-1 and Isl-1. Tlx-1 is dramatically down-regulated during this process, indicating that this tissue is reprogrammed from a splenic to pancreatic endocrine fate. Finally, an attempt to augment splenic iMET is made through the addition of a Wnt agonist. These findings, together with the recent discovery that the mature human spleen contains Tlx-1 positive cells, may be a useful target for future bench-to-bedside translation strategies for this work. Therefore, the spleen may be an ideal future tissue source for islet transplantation to treat patients with T1DM.
6
FernaÌndez, Serra Montserrat. "Role of the MAPK signalling pathway in the epithelial mesenchyme transition in the sea urchin embryo." Thesis, Open University, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.441145.
Full text
7
Qiao, Bin. "Epithelial-Mesenchymal Transition and Mesenchymal-Epithelial Transition in Oral Stem Cell Carcinogenesis." Thesis, Griffith University, 2011. http://hdl.handle.net/10072/367467.
Full textAbstract:
Oral squamous cell carcinoma (OSCC), derived from normal oral epithelium transformation, remains a major public health problem world-wide. The prognosis of OSCCs that occur on lips is good, while other sites of oral mucosa where OSCC appears are more progressive, invasive and metastatic. A small subset of cells within a malignant neoplasm, named cancer stem cells (CSCs) or tumour initiating cells are thought to be capable of initiating the neoplasm itself, and of driving its growth and recurrance after treatment. The precise origin of CSCs is an ambiguous issue at present. The first proposal of the origin of CSCs is that CSCs develop from tumour cells themselves via cellular dedifferentiation. The secondary hypothesis for the origin of CSCs proposes that CSCs are the product of malignant transformation of adult stem cells. In this Ph.D thesis, we tried to demonstrate that CSCs in OSCC may be produced from those pathways.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Medicine
Griffith Health
Full Text
8
Robson, Ewan John Douglas. "Characterisation of epithelial-mesenchymal transition in murine mammary epithelial cells." Thesis, University of Cambridge, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.616130.
Full text
9
Millanes, Romero Alba 1986. "Heterochromatin dynamics during epithelial-to-mesenchymal transition." Doctoral thesis, Universitat Pompeu Fabra, 2014. http://hdl.handle.net/10803/129339.
Full textAbstract:
Although heterochromatin is enriched with repressive traits, it is actively transcribed, giving
rise to large amounts of non-coding RNAs. These transcripts are responsible for the formation
and maintenance of heterochromatin, but little is known about how their transcription is
regulated. In this thesis we show that Snail1 transcription factor represses mouse
pericentromeric transcription and regulates heterochromatin organization through the action
of the H3K4 deaminase LOXL2. Snail1 has a key role in epithelial-to-mesenchymal transition
(EMT). We show that, also during this process, Snail1 is responsible for pericentromeric
transcription regulation. At the onset of EMT, one of the major structural heterochromatin
proteins, HP1α, is transiently released from heterochromatin foci in a Snail1/LOXL2 dependent
manner, concomitantly with a down-regulation of major satellite transcription. Moreover,
prevention of major satellite transcripts down-regulation compromises the migratory and
invasive behaviour of EMT resulting mesenchymal cells. We propose that Snail1 and LOXL2
regulate heterochromatin during this process, which may be crucial to allow the genome
reorganization required to complete EMT.Tot i estar enriquida en marques repressores, l’heterocromatina es transcriu activament i dóna lloc a grans quantitats d’ARNs no codificants. Aquests trànscrits són responsables de la formació i el manteniment de l’heterocromatina, però com es regula la seva transcripció segueix sent quelcom poc clarificat. En aquesta tesi demostrem que el factor de transcripció Snail1 reprimeix la transcripció pericentromèrica en cèl·lules de ratolí i regula l’organització de l’heterocromatina a través de l’acció de la LOXL2, que deamina l’H3K4. Snail1 té un paper clau en la transició epiteli-mesènquima (EMT). Aquí demostrem que, també durant aquest procés, Snail1 és responsable de la regulació de la transcripció pericentromèrica. A l’inici de l’EMT, l’HP1α, una de les principals proteïnes estructurals de l’heterocromatina, es desprèn de forma transitòria de l’heterocromatina. Aquest esdeveniment està regulat per Snail1 i LOXL2 i coincideix amb una disminució de la transcripció pericentromèrica. El bloqueig de la baixada dels trànscrits durant l’EMT compromet les capacitats migratòries i invasives de les cèl·lules mesenchimals que en resulten. Així doncs, proposem que Snail1 i LOXL2 regulen l’heterocromatina durant aquest procés, i així permeten que tingui lloc la reorganització genòmica que deu ser necessària per tal que es completi la EMT.
10
Brocchieri, Cristian. "A study on the regulation of Epithelial to Mesenchymal Transition in the Ovarian Surface Epithelium." Thesis, University of Cambridge, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.611315.
Full text
11
Carter, Lauren. "Defining the Epithelial-to-Mesenchymal Transition and Regulation of Stemness in the Ovarian Surface Epithelium." Thesis, Université d'Ottawa / University of Ottawa, 2018. http://hdl.handle.net/10393/38491.
Full textAbstract:
The ovarian surface epithelium (OSE) is a monolayer of cells surrounding the ovary that is ruptured during ovulation. After ovulation the wound is repaired, however this process, and the mechanisms to maintain OSE homeostasis after the wound is repaired are poorly understood. We have shown the mouse OSE (mOSE) contains a stem cell population that is expanded by Transforming Growth Factor Beta 1 (TGFB1), a factor present in follicular fluid. These data suggest that components in the follicular fluid such as TGFB1 may promote wound repair and OSE homeostasis through maintenance of the OSE stem cell population. Additionally, TGFB1 may promote wound repair through induction of an epithelial-to-mesenchymal transition (EMT) and activation of pro-survival pathways, as seen in other tissues.
To elucidate the mechanism for TGFB1-mediated ovulatory wound repair, mOSE cells were treated with TGFB1, which induced an EMT seen with increased Snai1 expression and cell migration. Snai1 overexpression also increased cell migration and sphere formation (a stem cell characteristic). RNA sequencing results suggest this is at least in part through elevated collagen deposition in SNAI1 overexpressing cells. A TGFB signalling targets array identified Cox2 induction following TGFB1 treatment. Constitutive Cox2 expression did not promote an EMT, but enhanced sphere formation and cell survival. Finally, TGFB1 treatment decreased Brca1 expression, which when deleted from mOSE cells also increased sphere formation. RNA sequencing results suggest that Brca1 deletion promotes stemness through activation of the stem cell genes Ly6a and Lgr5. RNA sequencing was also used to compare mOSE cells cultured as monolayers and as spheroids, with and without TGFB1. These results validate our findings that TGFB1 promotes an EMT partially through Snail induction and the upregulation of Cox2. mOSE cells cultured as spheroids acquire a mesenchymal transcriptional profile that is further enhanced with TGFB1 treatment.
These data suggest that TGFB1 may promote ovulatory wound repair and maintain OSE homeostasis through the induction of an EMT, maintenance of the stem cell population and activation of a pro-survival pathway. Interestingly, mOSE spheroids also decrease Brca1 expression and upregulate cancer associated genes such as Pax8 and Greb1. The induction of survival pathways, while simultaneously increasing stemness and repressing Brca1 could render cells more susceptible to transformation. This work provides novel insights as to why ovulation is the primary non-hereditary risk factor for ovarian cancer.
12
Tan, E.-Jean. "Transcriptional and Epigenetic Regulation of Epithelial-Mesenchymal Transition." Doctoral thesis, Uppsala universitet, Ludwiginstitutet för cancerforskning, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-206120.
Full textAbstract:
The transforming growth factor beta (TGFβ) is a cytokine that regulates a plethora of cellular processes such as cell proliferation, differentiation, migration and apoptosis. TGFβ signals via serine/threonine kinase receptors and activates the Smads to regulate gene expression. Enigmatically, TGFβ has a dichotomous role as a tumor suppressor and a tumor promoter in cancer. At early stages of tumorigenesis, TGFβ acts as a tumor suppressor by exerting growth inhibitory effects and inducing apoptosis. However, at advanced stages, TGFβ contributes to tumor malignancy by promoting invasion and metastasis. The pro-tumorigenic TGFβ potently triggers an embryonic program known as epithelial-mesenchymal transition (EMT). EMT is a dynamic process whereby polarized epithelial cells adapt a mesenchymal morphology, thereby facilitating migration and invasion. Downregulation of cell-cell adhesion molecules, such as E-cadherin and ZO-1, is an eminent feature of EMT. TGFβ induces EMT by upregulating a non-histone chromatin factor, high mobility group A2 (HMGA2). This thesis focuses on elucidating the molecular mechanisms by which HMGA2 elicits EMT. We found that HMGA2 regulates a network of EMT transcription factors (EMT-TFs), such as members of the Snail, ZEB and Twist families, during TGFβ-induced EMT. HMGA2 can interact with Smad complexes to synergistically induce Snail expression. HMGA2 also directly binds and activates the Twist promoter. We used mouse mammary epithelial cells overexpressing HMGA2, which are mesenchymal in morphology and highly invasive, as a constitutive EMT model. Snail and Twist have complementary roles in HMGA2-mesenchymal cells during EMT, and tight junctions were restored upon silencing of both Snail and Twist in these cells. Finally, we also demonstrate that HMGA2 can epigenetically silence the E-cadherin gene. In summary, HMGA2 modulates multiple reprogramming events to promote EMT and invasion.
13
Abdulla, Tariq. "Advances in modelling of epithelial to mesenchymal transition." Thesis, Loughborough University, 2013. https://dspace.lboro.ac.uk/2134/12744.
Full textAbstract:
Epithelial to Mesenchymal Transition (EMT) is a cellular transformation process that is employed repeatedly and ubiquitously during vertebrate morphogenesis to build complex tissues and organs. Cellular transformations that occur during cancer cell invasion are phenotypically similar to developmental EMT, and involve the same molecular signalling pathways. EMT processes are diverse, but are characterised by: a loss of cell-cell adhesion; a gain in cell-matrix adhesion; an increase in cell motility; the secretion of proteases that degrade basement membrane proteins; an increased resistance to apoptosis; a loss of polarisation; increased production of extracellular matrix components; a change from a rounded to a fibroblastic morphology; and an invasive phenotype. This thesis focuses explicitly on endocardial EMT, which is the EMT that occurs during vertebrate embryonic heart development. The embryonic heart initially forms as a tube, with myocardium externally, endocardium internally, with these tissue layers separated by a thick extracellular matrix termed the cardiac jelly. Some of the endocardial cells in specific regions of the embryonic heart tube undergo EMT and invade the cardiac jelly. This causes cellularised swellings inside the embryonic heart tube termed the endocardial cushions. The emergence of the four chambered double pump heart of mammals involves a complex remodelling that the endocardial cushions play an active role in. Even while heart remodelling is taking place, the heart tube is operating as a single-circulation pump, and the endocardial cushions are performing a valve-like function that is critical to the survival of the embryo (Nomura-Kitabayashi et al. 2009). As the endocardial cushions grow and remodel, they become the valve leaflets of the foetal heart. The endocardial cushions also contribute tissue to the septa (walls) of the heart. Their correct formation is thus essential to the development of a fully functional, fully divided, double-pump system. It has been shown that genetic mutations that cause impaired endocardial EMT lead to the development of a range of congenital heart defects (Fischer et al. 2007). An extensive review is conducted of existing experimental investigations into endocardial EMT. The information extracted from this review is used to develop a multiscale conceptual model of endocardial EMT, including the major protein signalling pathways involved, and the cellular phenotypes that they induce or inhibit. After considering the requirements for computational simulations of EMT, and reviewing the various techniques and simulation packages available for multi-cell modelling, cellular Potts modelling is selected as having the most appropriate combination of features. The open source simulation platform Compucell3D is selected for model development, due to the flexibility, range of features provided and an existing implementation of multiscale models; that include subcellular models of reaction pathways. Based on the conceptual model of endocardial EMT, abstract computational simulations of key aspects are developed, in order to investigate qualitative behaviour under different simulated conditions. The abstract simulations include a 2D multiscale model of Notch signalling lateral induction, which is the mechanism by which the embryonic heart tube is patterned into cushion and non-cushion forming regions. Additionally, a 3D simulation is used to investigate the possible role of contact-inhibited mitosis, upregulated by the VEGF protein, in maintaining an epithelial phenotype. One particular in vitro investigation of endocardial EMT (Luna-Zurita et al. 2010) is used to develop quantitative simulations. The quantitative data used for fitting the simulations consist of cell shape metrics that are derived from simple processing of the imaging results. Single cell simulations are used to investigate the relationship between cell motility and cell shape in the cellular Potts model. The findings are then implemented in multi-cell models, in order to investigate the relationship between cell-cell adhesion, cell-matrix adhesion, cell motility and cell shape during EMT.
14
De, Arpan. "Circadian clock regulation of epithelial-mesenchymal and mesenchymal-epithelial transitions in glioma and breast cancer cells." Bowling Green State University / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1566494866910786.
Full text
15
Ilter, Didem. "The Role of ERK2 in Regulating Epithelial-Mesenchymal Transition." Thesis, Harvard University, 2014. http://dissertations.umi.com/gsas.harvard:11407.
Full textAbstract:
Epithelial-mesenchymal transition (EMT) is a fundamental developmental program, which is believed to be reactivated during the progression of in situ carcinoma to aggressive metastatic cancers. Ras-ERK pathway has been shown to play a crucial role in EMT. We have previously shown that ERK2, but not ERK1, is necessary for RasV12-induced EMT and overexpression of ERK2 is sufficient to promote EMT. ERK2 promotes EMT by regulating several factors, including the upregulation of transcription factors ZEB1/2. ZEB1/2 repress expression of E-cadherin, which is necessary for polar epithelial tissue formations.
16
Dubois-Marshall, Sylvie. "Understanding epithelial to mesenchymal transition in human breast cancer." Thesis, University of Edinburgh, 2012. http://hdl.handle.net/1842/24541.
Full textAbstract:
Background and aims: Increasing evidence suggests that epithelial to mesenchymal transition (EMT) has a key role in breast cancer progression, underlying invasion, metastatic dissemination and acquisition of therapeutic resistance. However, this role is predominantly inferred from in vitro and animal studies and controversy regarding EMT in human cancer remains. This thesis has two principle aims. Firstly, to clarify the role of EMT in human breast cancer at the protein level. Secondly, to develop a three-dimensional in vitro assay to investigate cell invasion. Experimental Design: Two independent patient cohorts of high-grade, invasive ductal breast cancer were interrogated for their expression of key EMT proteins using quantitative immunofluorescence. This analysis was extended to paired lymph node metastases for a subset of cases. EMT-related cell lines were selected based on gene and protein expression data. These lines were investigated using lightmicroscopy, immunohistochemistry and immunofluorescence in a three-dimensional assay that models invasion across the basement membrane. Results: Two transcriptionally-driven EMT programmes were identified. One comprises vimentin, Snail and Slug and is uncoupled from E-cadherin downregulation. A second is characterised by up-regulation of WT1, Snail and Slug and down-regulation of E-cadherin. Importantly, acquisition of this phenotype in lymph node metastases predicts poor outcome. Some aspects of these programmes were recapitulated in vitro. Conclusions: These results suggest that EMT does occur in human breast cancer but in a manner distinct to that seen in vitro. The examination of primary tumours with their paired lymph node metastases may significantly contribute to understanding EMT. Lastly, in vitro models can reflect aspects of tumour biology and may prove invaluable in identifying clinically relevant, targetable pathways.
17
Peng, Zhengang, Jennifer Weber, Zhaosheng Han, Rulong Shen, Wenchao Zhou, James Scott, Michael Chan, and Huey-Jen Lin. "Dichotomy effects of Akt signaling in breast cancer." BioMed Central, 2012. http://hdl.handle.net/10150/610205.
Full textAbstract:
BACKGROUND:The oncogenic roles contributed by the Akt/PKB kinase family remain controversial and presumably depend on cell context, but are perceived to be modulated by an interplay and net balance between various isoforms. This study is intended to decipher whether distinct Akt kinase isoforms exert either redundant or unique functions in regulating neoplastic features of breast cancer cells, including epithelial-mesenchymal transition (EMT), cell motility, and stem/progenitor cell expansion.RESULTS:We demonstrate that overactivation of Akt signaling in nonmalignant MCF10A cells and in primary cultures of normal human mammary epithelial tissue results in previously unreported inhibitory effects on EMT, cell motility and stem/progenitor cell expansion. Importantly, this effect is largely redundant and independent of Akt isoform types. However, using a series of isogenic cell lines derived from MCF-10A cells but exhibiting varying stages of progressive tumorigenesis, we observe that this inhibition of neoplastic behavior can be reversed in epithelial cells that have advanced to a highly malignant state. In contrast to the tumor suppressive properties of Akt, activated Akt signaling in MCF10A cells can rescue cell viability upon treatment with cytotoxic agents. This feature is regarded as tumor-promoting.CONCLUSION:We demonstrate that Akt signaling conveys novel dichotomy effects in which its oncogenic properties contributes mainly to sustaining cell viability, as opposed to the its tumor suppressing effects, which are mediated by repressing EMT, cell motility, and stem/progenitor cell expansion. While the former exerts a tumor-enhancing effect, the latter merely acts as a safeguard by restraining epithelial cells at the primary sites until metastatic spread can be moved forward, a process that is presumably dictated by the permissive tumor microenvironment or additional oncogenic insults.
18
Porta, de la Riva Montserrat. "Transcriptional activation induced by snail 1 during epithelial-mesenchymal transition." Doctoral thesis, Universitat Pompeu Fabra, 2009. http://hdl.handle.net/10803/7205.
Full textAbstract:
La transició epiteli-mesènquima (TEM) és un procés en què cèl lules epitelials, immòbils i amb polaritat apico-basal transiten cap un fenotip mesenquimal o fibroblàstic. L'expressió del factor de transcripció snail1 és suficient per induir TEM en cèl lules en cultiu i és necessari per la majoria de les TEM fisiològiques descrites. Snail1 és un membre de la família de proteïnes amb dits de Zinc que reprimeix gens epitelials (com l'E-cadherina) a través de la unió directa a seqüències especifiques dels promotors anomenades caixes E i posterior reclutament de corepressors. La TEM també es caracteritza per l'activació de gens mesenquimals, però el mecanisme pel qual snail1 indueix l'expressió d'aquests és poc conegut. En aquest treball demostrem que snail1 actua a nivell transcripcional per incrementar els nivells dels marcadors mesenquimals FN1 (fibronectina) i LEF1 (de l'anglès, lymphoid enhancer-binding factor 1) a través d'un mecanisme nou per aquesta proteïna de dits de Zn que no requereix ni caixes E ni unió directa a l'ADN. A més a més, mostrem que, per a dur a terme l'activació, snail1 coopera amb dos factors de transcripció ja descrits en relació a la TEM: beta-catenina i NF-kappa-B. Els nostres resultats també proven que l'expressió forçada de la E-cadherina evita aquesta cooperació i conseqüent activació gènica. A banda d'aquest mecanisme, també hem descrit que el factor de transcripció TFCP2c, que no havia estat prèviament relacionat amb TEM, és necessari per l'activació del gen FN1 induïda per snail1.
Epithelial-mesenchymal transition (EMT) is a cellular process by which no motile epithelial, apico-basal-polarized cells transit towards a motile mesenchymal front-backpolarized phenotype. Expression of the transcription factor snail1 is sufficient to induce EMT in cultured cells and it is required for most of the physiological EMTs described. Snail1 is a member of the Zn finger protein family that represses epithelial genes (such as E-cadherin) by directly binding to specific promoter sequences called E-boxes and subsequent recruitment of corepressors. EMT is also accompanied by activation of mesenchymal genes, however, little is known of how snail1 induces their expression.
In this work we provide evidence that snail1 acts at the transcriptional level to increase the levels of the mesenchymal FN1 (fibronectin) and LEF1 (lymphoid enhancer-binding factor 1) genes through a novel mechanism for this Zn finger protein that does not require neither E-boxes nor direct binding to DNA. Furthermore, we describe a cooperative action in such mechanism between snail1 and two transcription factors previously related to EMT: beta-catenin and NF-kappaB. Our results also show that restoration of E-cadherin levels prevents such cooperation and subsequent activation. In addition, we also demonstrate that TFCP2c, which had not been previously linked to EMT, is also required for snail1-induced transcriptional activation of the FN1 gene.
19
Chandler, Heather Lynn. "Epithelial-mesenchymal transition in the anterior segment of the eye." Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1154533588.
Full text
20
Rygiel, Karolina Anna. "Epithelial to mesenchymal transition : a possible route to liver fibrogenesis." Thesis, University of Newcastle Upon Tyne, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.506551.
Full text
21
Perera, Nirmal. "The role of YAP 1 in regulating epithelial-mesenchymal transition." Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/10024780/.
Full textAbstract:
The Yes-associated protein 1 (YAP1) is an oncogenic transcriptional co-activator, which is negatively regulated by the Hippo signalling pathway. If the Hippo pathway is deregulated, YAP1 can translocate to the nucleus where it interacts with various transcription factors to drive transcription. Suppressing YAP1 as a therapeutic strategy has attracted considerable interest, especially since YAP1 and oncogenic RAS have been shown to interact in different tumour models. I evaluated the role(s) of YAP1 in transforming non-tumourigenic epithelial cells along the epithelial-mesenchymal transition (EMT) spectrum. Using a tetracycline-inducible expression system, I found that induced YAP1 overexpression in non-tumourigenic mouse Eph4 cells resulted in the upregulation of the mesenchymal markers, demonstrating a partial EMT. As a comparison, H-RAS overexpression in Eph4 cells resulted in E-CADHERIN relocalization away from the cell-cell junctions, also demonstrating a partial EMT. Co- expression of H-RAS and YAP1 resulted in a transition further along the EMT spectrum. However, YAP1 overexpression alone did not enhance cell migration or proliferation, whereas single overexpression of H-RAS did. Therefore, mutations which lead to overexpression of oncogenic RAS can be considered ‘driver’ mutations as they confer a significant tumourigenic potential to cancer cells. In contrast, although the upregulation of mesenchymal markers by YAP1 may also confer a survival advantage, YAP1 overexpression is not sufficient to trigger E-CADHERIN relocalization. Thus, mutations leading to YAP1 overexpression are neither ‘driver’ or ‘passenger’ mutations. Instead mutations leading to YAP1 overexpression are likely to represent an intermediate between a ‘driver’ and ‘passenger’ mutation. Hence I am referring to them as a ‘co-pilot’ of tumourigenesis.
22
Kah, Kong Jie. "ZEB1 is a central mediator of the Epithelial-Mesenchymal Transition." Thesis, Massachusetts Institute of Technology, 2012. http://hdl.handle.net/1721.1/72930.
Full textAbstract:
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2012.Vita. Cataloged from PDF version of thesis.
Includes bibliographical references.
Carcinomas are solid tumors arising from epithelial tissue, and account for the majority of cancer deaths in the United States. In most occurrences of carcinoma, it is the metastases that kill, not the primary tumor. The Epithelial-Mesenchymal Transition (EMT) provides a model by which tightly associated epithelial cancer cells can disseminate to distant sites. Many factors are known to trigger the EMT, but the extent to which the observed phenotypes represent a common process is unknown. There is also little appreciation of the extent to which EMT-inducing factors interact with one another or act on common or redundant pathways. In this study, I sought a common gene expression signature of the EMT by comparing five mesenchymal cell lines independently derived from the same parental epithelial line using different EMT-inducing factors. The resultant EMT core signature strongly suggested a common pathway is involved. Bioinformatics analysis revealed the transcription factor ZEBI to be a possible mediator of this common pathway. ZEB1 was found to be both sufficient to induce EMT and necessary for maintaining the mesenchymal phenotype in the same cells. ZEBI and miR-200 were known to reciprocally regulate each other, but their relative importance to the EMT phenotype had never been directly tested. I found that ZEB1 induced EMT regardless of miR-200c levels, thereby excluding the model in which miR-200c downregulation is a necessary step for the EMT. I also show evidence that EMT induced by the transcription factor Snail works at least in part through ZEB1.
by Kong Jie Kah.
Ph.D.
23
Hussey, George S. "Identification of a Post-Transcriptional Mechanism Regulating Epithelial-Mesenchymal Transition." Cleveland State University / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=csu1354051158.
Full text
24
Kim, Taewan. "The function of microRNAs in p53-regulated epithelial-mesenchymal transition." The Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1322493623.
Full text
25
Nakajima, Sanae. "N-cadherin expression and epithelial mesenchymal transition in pancreatic carcinoma." Kyoto University, 2007. http://hdl.handle.net/2433/135910.
Full text
26
Stylianou, Nataly. "Investigating the role of the epithelial-mesenchymal plasticity in prostate cancer." Thesis, Queensland University of Technology, 2017. https://eprints.qut.edu.au/107979/1/Nataly_Stylianou_Thesis.pdf.
Full textAbstract:
This thesis was a step forward in better understanding the involvement of cancer cell plasticity in the progression of prostate cancer to aggressive disease. These studies described for the first time the transcriptional landscape of epithelial-mesenchymal plasticity in prostate cancer which led to the discovery of a molecular signature capable of identifying high-risk patients. In addition, this project revealed new-found molecular targets that may regulate cancer cell plasticity, thus making them attractive therapeutic options for patients with prostate cancer.
27
Bozić, Stanojević Milica. "Glutamatergic signaling in proximal tubular cells maintains the epithelial phenotype and decreases epithelial-mesenchymal transition." Doctoral thesis, Universitat de Lleida, 2011. http://hdl.handle.net/10803/51013.
Full text
28
Monsor, Rehanna. "The role of the IGF axis in epithelial to mesenchymal transition in prostate epithelial cells." Thesis, University of Bristol, 2017. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.723508.
Full text
29
Gorowiec, Marta Roksana. "The role of oxidative stress in lung epithelial cells undergoing epithelial-to-mesenchymal transition (EMT)." Thesis, University of Newcastle Upon Tyne, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.512043.
Full text
30
Abdulkareem, Ali Abbas. "Potential involvement of epithelial-mesenchymal transition in the pathogenesis of periodontitis." Thesis, University of Birmingham, 2017. http://etheses.bham.ac.uk//id/eprint/7340/.
Full textAbstract:
Epithelial-mesenchymal transition is reportedly important in loss of epithelial integrity and cell migration in inflammatory/infectious diseases and cancer. Since Gram negative anaerobic periodontal pathogens are well-recognized to induce intense inflammatory responses; the present study investigated their ability to induce EMT in vitro. A 2D chronic inflammatory model was developed using either the H400 oral keratinocyte cell-line or primary rat oral keratinocytes which were exposed to heat-killed Fusobacterium nucleatum, Porphyromonas gingivalis and Escherichia coli LPS for up to 8-days. EMT-associated changes were determined using semi-quantitative-RT-PCR, PCR-arrays, ELISA, scratch/transwell migration assays, immunocytochemistry/immunofluorescence, and transepithelial electrical resistance. Chronically stimulated cultures increased extracellular levels of the EMT regulatory cytokines, TGF-β1, TNF-α and EGF, whilst subsequent EMT-induction was indicated by up-regulation of mesenchymal markers, including vimentin and N-cadherin, and concomitant down-regulation of epithelial markers including E-cadherin and β-catenin. In addition, intracellular signaling activity of key EMT regulatory transcription factors, Snail-1 and NF-ĸB, increased following chronic bacterial exposure and was associated with enhanced cellular migratory activity and reduced epithelial barrier integrity. These results indicated for the first time that EMT may be involved in the compromised epithelial barrier function observed during periodontitis pathogenesis which may occur in response to prolonged local bacterial exposure.
31
Jager, Michal. "The role of aortic carboxypeptidase-like protein in epithelial-mesenchymal transition." Thesis, Boston University, 2012. https://hdl.handle.net/2144/12428.
Full textAbstract:
Thesis (M.A.)--Boston University
PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.Communication from stromal cells to tumors contributes to the progression of several carcinomas. Stromal fibroblasts, also referred to as cancer associated fibroblasts, in part through their production of secreted factors, promote epithelial-mesenchymal transition (EMT). EMT contributes to cancer progression by disseminating cells from the primary tumor and increasing these cells migratory capacity, an initial step in metastasis. Recently, several microarray studies have identified aortic carboxypeptidase-like protein (ACLP) as being significantly up-regulated in cancers, including prostate cancer and breast cancer, leading to the hypothesis that ACLP may regulate tumor progression and metastasis. To begin to test this hypothesis, this study first examined ACLP expression in a mouse mammary ductal carcinoma model and detected abundant ACLP expression in the cells surrounding the tumor. Cultured fibroblasts, derived from these tumors, readily expressed and secreted ACLP. To explore the functional contribution of ACLP to EMT in vitro we treated normal murine mammary gland epithelial cells (NMuMG) with recombinant ACLP (rACLP). In NMuMG cells, rACLP modulated the expression of epithelial-mesenchymal transition markers, Snail, fibronectin, occludin, and a-smooth muscle actin. Furthermore, rACLP treatment resulted in E-cadherin dissolution from the cell surface when compared with controls. These studies indicate that fibroblasts within a breast carcinoma express and may secrete ACLP, and in vitro data demonstrate that rACLP is capable of promoting EMT in normal epithelial cells. Therefore, ACLP may serve as an important mediator in the progression of cancer.
32
Scott, Lewis. "Mechanochemical Regulation of Epithelial Tissue Remodeling: A Multiscale Computational Model of the Epithelial-Mesenchymal Transition Program." VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/6032.
Full textAbstract:
Epithelial-mesenchymal transition (EMT) regulates the cellular processes of migration, growth, and proliferation - as well as the collective cellular process of tissue remodeling - in response to mechanical and chemical stimuli in the cellular microenvironment. Cells of the epithelium form cell-cell junctions with adjacent cells to function as a barrier between the body and its environment. By distributing localized stress throughout the tissue, this mechanical coupling between cells maintains tensional homeostasis in epithelial tissue structures and provides positional information for regulating cellular processes. Whereas in vitro and in vivo models fail to capture the complex interconnectedness of EMT-associated signaling networks, previous computational models have succinctly reproduced components of the EMT program. In this work, we have developed a computational framework to evaluate the mechanochemical signaling dynamics of EMT at the molecular, cellular, and tissue scale. First, we established a model of cell-matrix and cell-cell feedback for predicting mechanical force distributions within an epithelial monolayer. These findings suggest that tensional homeostasis is the result of cytoskeletal stress distribution across cell-cell junctions, which organizes otherwise migratory cells into a stable epithelial monolayer. However, differences in phenotype-specific cell characteristics led to discrepancies in the experimental and computational observations. To better understand the role of mechanical cell-cell feedback in regulating EMT-dependent cellular processes, we introduce an EMT gene regulatory network of key epithelial and mesenchymal markers, E-cadherin and N-cadherin, coupled to a mechanically-sensitive intracellular signaling cascade. Together these signaling networks integrate mechanical cell-cell feedback with EMT-associated gene regulation. Using this approach, we demonstrate that the phenotype-specific properties collectively account for discrepancies in the computational and experimental observations. Additionally, mechanical cell-cell feedback suppresses the EMT program, which is reflected in the gene expression of the heterogeneous cell population. Together, these findings advance our understanding of the complex interplay in cell-cell and cell-matrix feedback during EMT of both normal physiological processes as well as disease progression.
33
Walia, Vijay. "hCLCA2 IS A p53-REGULATED GENE REQUIRED FOR MESENCHYMAL TO EPITHELIAL TRANSITION IN BREAST." OpenSIUC, 2010. https://opensiuc.lib.siu.edu/dissertations/131.
Full textAbstract:
The breast tumor suppressor hCLCA2 is a putative chloride regulator that is expressed in normal breast epithelial cells and frequently down-regulated in breast cancers. The first CLCA protein was described as a calcium-activated, plasma-membrane chloride channel having four or five transmembrane pass structure that could form a channel pore. However, CLCA topology is inconsistent with chloride channel function. We showed that hCLCA2 itself is unlikely to form a channel as it has only a single transmembrane segment with a short cytoplasmic tail and is mostly extracellular. Moreover, the N-terminal 109-kDa ectodomain is cleaved at the cell surface and shed into the medium while the 35-kDa C-terminal product is retained by the cell membrane. The general goal of my project was to study the function of this novel protein and its role in breast cancer. In addition to its role in chloride regulation, hCLCA2 behaves as a tumor suppressor gene that is frequently down-regulated in breast cancer. We previously demonstrated that murine homologs of hCLCA2 are transcriptionally induced during mammary involution, when the gland shuts down and 80% of the mammary epithelial cells die by apoptosis. In cell culture, conditions that cause G1 arrest such as contact inhibition and depriving cells of growth factors and anchorage induced these genes. Therefore, one of the goals of this project was to find if this is true of hCLCA2 in human breast epithelial cells. We found that hCLCA2 was induced by the above mentioned stresses and by pharmacological blockage of cell survival signaling. In addition, we found that DNA-damaging agents doxorubicin and aphidicolin potently induced hCLCA2 in p53-positive cell lines such as MCF-7 but not in p53-deficient cells such as MDA-MB231. An adenovirus encoding p53 induced hCLCA2 expression in a broad spectrum of breast cancer cell lines while a control virus did not, suggesting that hCLCA2 is a p53-inducible gene. To further test the hypothesis, we performed chromatin immunoprecipitation (ChIP) to determine whether p53 bound to the hCLCA2 promoter. This analysis showed that p53 binds directly to the hCLCA2 promoter between -157 and -359bp upstream of the translation initiation site. This segment was required for the p53-dependent expression of an hCLCA2-luciferase fusion gene. Point mutation of the p53 consensus binding motif abolished this induction. Induction of hCLCA2 in MCF-7 cells by doxorubicin was inhibited by p53 knockdown and by p53 inhibitor pifithrin, indicating that p53 activates the endogenous hCLCA2 promoter in response to DNA damage. An adenovirus encoding hCLCA2 induced a cell cycle lag in G0/G1 phase, decreased intracellular pH from 7.49 to 6.7, caused Bax and Bad translocation to the mitochondria, activated caspases, induced PARP cleavage, and promoted apoptosis. Conversely, hCLCA2 knockdown enhanced proliferation of epithelial MCF10A cells and reduced sensitivity to doxorubicin. These results reveal the molecular mechanism of hCLCA2 induction and downstream events that may provide protection from tumorigenesis. Epithelial cells acquire mesenchymal characteristics by undergoing phenotypic and genotypic changes during cancer progression. An early step in the epithelial to mesenchymal transition (EMT) is the disruption of intercellular connections due to loss of epithelial cadherins. We find that expression of tumor suppressor hCLCA2 is strongly associated with epithelial differentiation and that induction of EMT by mesenchymal transcription factors represses its expression. Moreover, we found that knockdown of hCLCA2 by RNA interference results in disruption of cell-cell junctions by downregulating E-cadherin. This also imparts invasiveness and anoikis-resistance to epithelial cells but is insufficient to induce full EMT. However, activation of Ras oncogene in combination with hCLCA2 knockdown is sufficient to induce full EMT in vitro. These findings indicate that, like E-cadherin, hCLCA2 is required for epithelial differentiation and that its loss during tumor progression may contribute to metastasis.
34
Laffin, Brian Edward. "Regulation of epithelial-mesenchymal transition and DNA damage responses by singleminded-2s." [College Station, Tex. : Texas A&M University, 2008. http://hdl.handle.net/1969.1/ETD-TAMU-3076.
Full text
35
Tse, Gina Chan. "The role of epithelial mesenchymal transition transcription factors on DNA damage response." Thesis, University of Leicester, 2016. http://hdl.handle.net/2381/38292.
Full textAbstract:
The role of epithelial mesenchymal transition (EMT) has been identified to influence many processes associated with cancer development; malignant transformation, invasion, resistance to therapeutics to name but a few. Despite this, little is known about the relationship between EMT and DNA damage response (DDR). This study aims to investigate how the EMT programs activated in different cancer cell backgrounds influence DDR. The understanding of this interrelationship will help in designing new therapies to combat forms of cancer in which EMT plays a role. Microarray data obtained in three different EMT cell models show a strong influence of EMT transcription factor (TF) expression on DDR genes. The role of DDR in the genome integrity allowed us to suggest that EMT is a determinant of genome instability. A novel link between ZEB2, cyclin D1 and DNA Ligase 1 has been identified, and we propose the expression of ZEB2 increases the concentration of unrepaired single strand breaks within cells. Further investigation reveals EMT-TFs reduce HR gene expression, suggesting that activation of EMT pathways may represent the mechanism underlying the formation of BRCAness phenotype in sporadic cancers. BRCAness predicts PARP inhibitor sensitivity; and this project identifies two cell models in which activation of EMT programs confers sensitivity to the PARP inhibitor olaparib. However, the role of EMT-TF in conferring sensitivity to PARP inhibition is not conclusive. Overall, this project has identified two potential sources of genomic instability imposed by the deficiencies in single strand and double strand break repair pathways, both enforced by EMT. This project concludes EMT does play role in DDR; and further investigation will be required to elucidate the exact mechanisms and therapeutic perspectives of these observations.
36
Cummings, Natalie Marie. "The role of epithelial mesenchymal transition in the progression of bronchial dysplasia." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.607647.
Full text
37
Volakis, Leonithas I. "Evaluating Dynamic Changes in Cancer Cell Mechanics during Epithelial to Mesenchymal Transition." The Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1492739871307445.
Full text
38
Block, C. James Garnet. "Investigation of the Common Epithelial-to-Mesenchymal Transition Program in Breast Cancer." Thesis, Wayne State University, 2022. http://pqdtopen.proquest.com/#viewpdf?dispub=27741360.
Full textAbstract:
The epithelial-to-mesenchymal transition (EMT) is a critical mechanism during the process of normal embryonic development and wound healing that can be pathologically re-activated during cancer progression. We hypothesized that comparing the transcriptional programs of multiple EMT-driving transcription factors (EMT-TFs) would identify a common set of critical EMT effectors. After elucidating this common transcriptional program, the commonly upregulated RNA binding protein RBMS3 was chosen as a target for functional validation. RBMS3 was both necessary and sufficient for EMT and breast cancer progression, demonstrating the validity of focusing on common EMT-associated effectors. Finally, by evaluating the associations of multiple EMT-TFs with the tumor microenvironment in several solid tumor types, ZEB1 and a ZEB1-regulated transcription program was identified as uniquely associated with immune suppression and poor prognosis. In conclusion, this study significantly advances both the understanding of the mechanisms underlying EMT and the distinct associations of different EMT-TFs with tumor biology and the tumor microenvironment.
39
Rao, Srinivasa Rao. "Novel signalling pathways regulating epithelial-mesenchymal transition in bone metastatic prostate cancer." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:bc90d3e0-420c-424f-b6ea-5567cbb21529.
Full textAbstract:
Prostate cancer (PCa) cells predominantly metastasize to bone and the complex crosstalk between PCa cells and osteoblasts (bone-forming cells) and osteoclasts (bone-destroying cells) leads to increased tumour growth and worsening of bone disease. Understanding the mechanisms of PCa bone metastasis can identify the aggressive fraction of PCa resulting in earlier intervention. The ability of PCa cells to express bone cell-specific features, termed osteomimicry, could potentially explain the osteotropic nature of PCa cells. The aim of this study was to determine the role of osteomimicry in the regulation of epithelial-mesenchymal transition (EMT) in bone metastatic prostate cancer cells. It was demonstrated that the osteoblast-specific marker alkaline phosphatase (bone/liver/kidney) (ALPL) was overexpressed in bone metastatic (ARCaPM), compared to non-metastatic (ARCaPE), human PCa cells. Knockdown of ALPL resulted in decreased cell viability, increased cell death and a change from mesenchymal to epithelial morphology in ARCaPM and PC3 cells, and increased CDH1 expression along with decreased migration in ARCaPM cells. Treatment with extracellular ATP also resulted in decreased viability, increased expression of epithelial markers (CDH1, KRT14) and decreased expression of mesenchymal markers (VIM, ZEB1), and reduced expression of ALPL in ARCaPM cells. Small RNA-sequencing identified microRNAs differentially expressed between ARCaPE and ARCaPM PCa cell lines: miR-373 expression was lower in ARCaPM compared to ARCaPE cells and its overexpression in ARCaPM cells resulted in a change to epithelial morphology, increased expression of the epithelial marker CDH1 and decreased expression of the mesenchymal markers VIM and ZEB1. Finally, the development of a high-throughput screening method to identify novel microRNA regulators of osteomimicry was described, which identified two microRNAs miR-199a-5p and miR-212 as positive regulators of ALP activity. Taken together, this thesis describes the identification of ALPL and ATP as novel regulators of epithelial-mesenchymal transition in PCa cells and high-throughput ALP-activity screening as a powerful tool to identify novel microRNA regulators of ALP expression.
40
Scholtes, Ben [Verfasser], and Gernot [Akademischer Betreuer] Zissel. "CCL18 als Induktor der "Epithelial to Mesenchymal Transition" im nicht-kleinzelligen Lungenkarzinom." Freiburg : Universität, 2013. http://d-nb.info/1123478201/34.
Full text
41
Zhai, Yubo. "REDEFINING THE MOLECULAR BASIS OF EPITHELIAL MESENCHYMAL TRANSITION IN BREAST CANCER METASTASIS." Master's thesis, Temple University Libraries, 2013. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/216586.
Full textAbstract:
BiochemistryM.S.
Metastasis is a multi-step process that begins with cancer cells migrating and invading away from the primary tumor site and extravasating into distant organs to establish a secondary tumor. The loss of epithelial expression markers by neoplastic breast cancer cells in the primary tumor is believed to play a pivotal role during breast cancer metastasis. This phenomenon is the hallmark of the epithelial mesenchymal transition (EMT) process. Gene expression microarrays were performed to investigate key functional elements on an in vitro metastasis model derived from human breast epithelial cells (MCF-10F) treated with 17-beta estradiol. Functional profiling of dysregulated genes revealed progressive changes in the integrin signaling pathway, and epithelial-mesenchymal transition. In tumorigenic cells, the levels of E-cadherin, desmoplakin and various keratins were low, whereas SLUG, integrin beta 1 and fibronectin were high. SLUG, a zinc finger transcription factor acting as a transcriptional repressor, was defined as a promising target which led us establishing a SLUG-centered hypothetical pathway from the profile of dysregulated genes.
Temple University--Theses
42
Griggs, Lauren. "FIBRONECTIN MECHANICS AND SIGNALING IN TGF-β1-INDUCED EPITHELIAL TO MESENCHYMAL TRANSITION." VCU Scholars Compass, 2018. https://scholarscompass.vcu.edu/etd/5539.
Full textAbstract:
Epithelial to Mesenchymal Transition (EMT) is a dynamic process by which a distinct change in the phenotype and function of epithelial cells render them as mesenchymal cells. Characteristics of mesenchymal cells include the ability to invade, increased migratory kinetics and heightened resistance to apoptosis. Therefore, there is a strong need to fully understand the mechanism for the induction of EMT in pathological conditions such as carcinoma progression. Recent advances highlight two pivotal contributors, soluble growth factor (gf) signals, and mechanical signals, in the process. However, to date, no clear mechanism exists linking the two in epithelial transdifferentiation. Transforming Growth Factor-β1 (TGF-β1), a gf known to induce EMT in breast cancer formation, induces EMT on rigid surfaces and apoptosis on compliant surfaces. It is our belief that a combination of mechanical signals, gf signals, and the type of extracellular matrix (ECM) proteins assembled by cells together drive the process of EMT. Here we investigated the role of the ECM protein fibronectin (FN) in EMT. Upon assembly into elastic, insoluble fibrils through cell-generated forces which become larger on stiffer surfaces, FN is able to serve as a gf delivery system. We examined the following hypothesis: Increased tissue stiffness drives FN assembly, which exposes cryptic binding sites for various gfs, such as TGF-β1, and creates a high concentration of these gfs at the cell surface, which in turn drives EMT. In this project we investigated three aims: (1) evaluate the effect of inhibiting FN fibrillogenesis and gf localization on TGF-β1-induced EMT, (2) assess the effect of TGF-β1 concentration on spatial patterning of ECM dynamics, cell phenotype and adherens junctional force, and (3) probe the role of the FN matrix in TGF-β1-induced spatial patterning of EMT. Results showed that both inhibition of FN fibril assembly and blocking the gf binding site on fibrils significantly attenuated the downstream effects of EMT. In microcontact patterns of epithelial colonies, increasing gf concentration led to spatial patterning of FN fibrils, cell phenotype and cell-cell junctional force. Elimination of FN fibrils effectively attenuated TGF-β1-induced spatial patterning. The knowledge acquired through these studies serves as an addition to an increasingly important body of work aimed at elucidating how physical changes within the microenvironment regulate physiology and pathology. By establishing a novel mechanism by which gf signaling induces EMT through interaction with the extracellular matrix, this research serves to combat the development and initiation of pathological phenomena, such as metastasis.
43
Upadhyaya, Akanksha. "Targeting epithelial to mesenchymal transition (EMT) to modulate prostate cancer cell chemoresistance." Thesis, Queensland University of Technology, 2020. https://eprints.qut.edu.au/201657/1/Akanksha_Upadhyaya_Thesis.pdf.
Full textAbstract:
Understanding why some cancer cells do not respond to chemotherapy is critical to developing new ways to control cancer. This project defined the important role of tumour cell plasticity in the response of prostate cancer cells to chemotherapy drugs. Key proteins that control cell plasticity have emerged as promising theranostic targets that can be pursued to develop new approaches to improve outcomes for men with metastatic prostate cancer.
44
Futterman, Matthew. "Evidence for partial epithelial-to-mesenchymal transition and recruitment of motile blastoderm edge cells during avian epiboly." Thesis, Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/39495.
Full textAbstract:
Embryonic epiboly has become an important developmental model for studying the mechanisms underlying collective movements of epithelial cells. In the last couple of decades, most studies of epiboly have utilized Xenopus or zebrafish as genetically tractable model organisms, while the avian epiboly model has received virtually no attention. Here, we re-visit epiboly in quail embryos and characterize several molecular markers of epithelial-to-mesenchymal transition (EMT) in the inner zone of the extraembryonic Area Opaca and at the blastoderm edge. Our results show that the intermediate filament vimentin, a widely-used marker of the mesenchymal phenotype, is strongly expressed in the edge cells compared to the cells in the inner zone, and that epiboly is inhibited when embryos are treated with Withaferin-A, a vimentin-targeting drug. Laminin, an extracellular matrix protein that is a major structural and adhesive component of the epiblast basement membrane, is notably absent from the blastoderm edge, and shows three distinct morphological regions approaching the leading edge. While these expression profiles are consistent with a mesenchymal phenotype, several other epithelial markers, including cytokeratin, β-catenin, and E-cadherin, were present in the blastoderm edge cells. Moreover, the results of a BrDU proliferation assay suggest that expansion of the edge cell population is primarily due to recruitment of cells from the inner zone, and not proliferation. Taken together, our data suggest that the edge cells of the avian blastoderm have characteristics of both epithelial and mesenchymal cells, and could serve as an in-vivo model for cancer and wound healing studies.
45
Zinn, Rabea Katharina [Verfasser], Henrik [Akademischer Betreuer] Ungefroren, and Heinz-Wolfram [Akademischer Betreuer] Bernd. "RAC1B : Wächter des epithelialen Phänotyps und Protektor gegen epitheliale-mesenchymale Transition / Rabea Katharina Zinn ; Akademische Betreuer: Henrik Ungefroren, Heinz-Wolfram Bernd." Lübeck : Zentrale Hochschulbibliothek Lübeck, 2021. http://d-nb.info/1230588310/34.
Full text
46
Sampaio, JoÃo Paulo Aguiar. "ImunoexpressÃo de Caderina-E no cÃncer colorretal primÃrio e nas metÃstases linfonodais." Universidade Federal do CearÃ, 2013. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=11260.
Full textAbstract:
A Caderina-E està intimamente relacionada com a transiÃÃo epitelial-mesenquimal e com a progressÃo tumoral em muitos tipos de cÃncer, inclusive no cÃncer colorretal. O objetivo deste trabalho foi avaliar a imunoexpressÃo de Caderina-E no cÃncer colorretal primÃrio e nas respectivas metÃstases linfonodais, na mucosa colÃnica normal, e investigar possÃveis correlaÃÃes desta expressÃo com parÃmetros clÃnicopatolÃgicos. Setenta e sete casos de colectomias por carcinoma colorretal e dez casos de linfonodos metastÃticos, dos arquivos do Departamento de Patologia e Medicina Legal/Universidade Federal do CearÃ, foram utilizados. Realizou-se o Tissue Microarray e imunohistoquÃmica, com anticorpo monoclonal anti-Caderina-E. Foram avaliados os seguintes escores: 0 = ausÃncia de expressÃo; 1 = expressÃo citoplasmÃtica; 2 = expressÃo mista (citoplasmÃtica e membranar); 3 = expressÃo membranar pura. Foi utilizada tanto a classificaÃÃo proposta por Jawhari et al., agrupando os casos em expressÃo anormal (escores 0, 1 e 2) e expressÃo normal (escore 3), como os critÃrios propostos por Almeida et al., agrupando os casos como expressÃo nÃo-membranar (escores 0 e 1) e expressÃo membranar (escores 2 e 3). Os tumores primÃrios tiveram mais casos de expressÃo de Caderina-E anormal em comparaÃÃo com a mucosa normal (p < 0.0001). NÃo houve diferenÃa significante entre expressÃo de Caderina-E no tumor intestinal e em metÃstases linfonodais, embora nestas a expressÃo membranar tenha sido mais freqÃente do que no sÃtio primÃrio. Tumores de cÃlulas agrupadas apresentaram maior expressÃo de Caderina-E membranar do que os de cÃlulas isoladas, tanto utilizando a classificaÃÃo de Jawhari et al. (p = 0.0230), como os critÃrios propostos por Almeida et al. (p = 0.0043). Em conclusÃo, a expressÃo anormal de Caderina-E no tumor primÃrio, com persistÃncia freqÃente da imunomarcaÃÃo membranar associada à marcaÃÃo citoplasmÃtica (marcaÃÃo anormal heterogÃnea ou mista), reforÃa as evidÃncias de que esta alteraÃÃo no cÃncer à mais qualitativa do que propriamente quantitativa. O predomÃnio da expressÃo membranar no sÃtio primÃrio da neoplasia e na metÃstase, com ou sem expressÃo citoplasmÃtica associada, principalmente em tumores de cÃlulas agrupadas, sugere que a presenÃa da Caderina-E à essencial para a invasÃo local e progressÃo tumoral, em oposiÃÃo ao clÃssico paradigma de que a progressÃo tumoral se exacerba com a perda desta molÃcula de adesÃo.E-cadherin is closely related to epitelial-mesenchymal transition and tumor progression in many cancers, including colorectal cancer. The aim of this study is to evaluate the expression of E-cadherin in primary colorectal cancer as well as in lymph node metastasis, establishing also a comparison with the expression of E-cadherin in normal colonic mucosa. We utilized 77 cases of colectomies for colorectal carcinoma and 10 cases of metastatic lymph nodes from the files of the Department of Pathology and Forensic Medicine/Federal University of Ceara. Tissue microarray and immunohistochemistry were performed with monoclonal anti-E-cadherin, evaluated using the following scores: 0 = no staining; 1 = cytoplasmic staining; 2 = mixed staining (cytoplasmic and membranous); 3 = membranous staining. It was used the classification proposed by Jawahri et al. which includes cases of abnormal expression (0, 1 and 2 scores) and cases of normal expression (3 score), and was also used the classification proposed by Almeida et al. which includes cases of non-membranous expression (0 and 1 scores) and membranous expression (2 and 3 scores). Primary tumors presented more cases of abnormal E-cadherin expression in comparison to normal colonic mucosa (p < 0.0001). There were no differences between E-cadherin expression in the primary tumor in comparison to lymph node metastasis. The grouped cell tumors showed increased expression of E-cadherin in comparison to isolated cell tumors, either using the classification proposed by Jawhari et al. (p = 0.0230) and the classification proposed by Almeida et al. (p = 0.0043). In conclusion, abnormal expression of E-cadherin in the primary tumor, with frequent membranar immunostaining associated with the cytoplasmic marking (abnormal heterogeneous or mixed staining), reinforces the evidence that E-cadherin expression change in cancer is more qualitative than quantitative. The predominance of membranar expression in primary tumor and lymph node metastasis, with or without associated cytoplasmatic expression, particularly in cell-grouped tumors, suggests that E-cadherin presence is essential for local invasion and tumor progression, as opposed to the classical paradigm that tumor progression is exacerbated by the loss of this adhesion molecule.
47
Wu, Shu-Yu. "Gene regulatory networks controlling an epithelial-mesenchymal transition." Diss., 2007. http://hdl.handle.net/10161/185.
Full text
48
"Functional characterization of CRMP1 in the epithelial-mesenchymal transition regulation in prostate cancer." 2013. http://library.cuhk.edu.hk/record=b5884413.
Full textAbstract:
Cai, Ganhui.Thesis (Ph.D.)--Chinese University of Hong Kong, 2013.
Includes bibliographical references (leaves 160-192).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Abstract also in Chinese.
49
Manhire-Heath, Rosemary. "Identification and analysis of regulators of the epithelial to mesenchymal transition using Drosophila wing disc eversion." Phd thesis, 2012. http://hdl.handle.net/1885/149752.
Full textAbstract:
The epithelial to mesenchymal transition (EMT), the process where epithelial cells break free from their adhesive connections and become migratory, is a key mechanism in development and disease. To discover new EMT regulators, wing disc eversion was developed as a model system to enable RNAi screening, in vivo, in Drosophila. During eversion, a population of wing imaginal disc cells, the peripodial cells, lose apico-basal polarity, adherens junctions, breakdown the basement membrane, then invade and migrate over larval cells to reestablish an epithelium. RNAi knockdown using peripodial drivers generates adult phenotypes ranging from thoracic clefts to internalised wings. In a screen of protein/lipid kinases and phosphatases, defects for genes involved in cell polarity, JNK and PI3Kinase signaling, cytokinesis, and novel genes were identified. In a similar screen of putative downstream targets of EMT associated pathways, a strong candidate was identified; the axonal guidance factor, netrinA (netA). Netrins are a family of chemoattractants with roles in migration, cell survival, and epithelial plasticity. A key Netrin receptor is the tumour suppressor DCC (Deleted in Colorectal Cancer), whose loss has been implicated in cancer progression through the promotion of cell survival. Loss of NetA or NetB in peripodial cells produced eversion failure and thoracic clefting. Two roles for Netrin in disc eversion were suggested by this study. Firstly a role in the later stages of thorax closure, in promoting the migration and integrity of the leading edge peripodial cells, post-EMT. In vitro disc culturing of netA RNAi discs revealed a significant reduction in eversion rates, suggesting a second role for NetA in the early stages of disc eversion, likely affecting the EMT. The Drosophila orthologue of DCC, Frazzled (Fra) was shown to antagonize this EMT process. Disc eversion is unaffected by fra RNAi knockdown but is disrupted by fra overexpression. The role of Fra as an antagonist correlates with its cellular localisation. In disc proper epithelia Fra localises to the cell cortex, whereas in peripodial cells Fra is reduced and localises to cytoplasmic puncta. When Fra is overexpressed it becomes enriched at the peripodial cell cortex and eversion is disrupted. The changes in levels and localisation of Fra are dependent on JNK and NetA signalling, both of which are required for disc eversion. Peripodial expression of dominant negative JNK restores Fra to the cell cortex while loss of NetA localizes Fra to the nucleus. Using disc eversion as model, a new EMT signaling pathway involving NetA and Fra was discovered. This study presented a role for NetA in promoting peripodial EMT while Fra was suggested to antagonize it. The work described here suggests that during disc eversion Fra may be involved in epithelial maintenance and that NetA may act as signal to allow EMT in Fra expressing epithelia. A possibility then could be that Fra prevents the progression of cancer not only by modulating cell survival, but also by promoting epithelial state to prevent EMT, thus acting as a suppressor of metastasis.
50
Zafar, Anjum. "Novel chromatin-associated role of Protein Kinase C family members in regulating inducible genes and microRNAs during epithelial to mesenchymal transition." Phd thesis, 2012. http://hdl.handle.net/1885/149888.
Full textAbstract:
The epithelial to mesenchymal transition (EMT) is a key step in cancer progression and metastasis. A small subpopulation of tumor cells formed thereby, referred to as Cancer Stem Cell (CSC) cells, potentially have a significant role for metastatic tumor initiation and recurrence. The epigenetic regulation underpinning control of gene expression programs in EMT and CSC formation processes are not well understood, largely because an appropriate inducible in vitro human model is lacking. This thesis describes the establishment of a novel human in vitro rapidly inducible breast cancer EMT model amenable to detailed analysis of epigenetic processes. The human breast cancer epithelial cell line, MCF-7 was stimulated with the PKC pathway inducer, PMA. This results in the emergence of a significant cancer stem cell-like subpopulation amidst almost complete mesenchymal conversion. The epithelial cells, CSC-like and non-CSC (NCSC) mesenchymal subpopulations were shown to be distinct in their transcriptional programs and microRNA profiles. The novel role of PKC isoforms as chromatin-associated enzymes in EMT and CSC formation processes has been indentified for the first time in this thesis. Chromatin immuno-precipitation (ChIP) assays revealed that non-phosphorylated PKC-theta predominated in the epithelial state across the promoter of uPAR, whilst phosphorylated PKC-thata predominated in the mesenchymal state of MCF-7 cells. In contrast, PKC-beta recruitment on the uPAR promoter predominated in mesenchymal state with little enrichment detected in the epithelial state. Similarly, phosphorylated H3T6, which is a surrogate for active PKC-beta was highly recruited in the mesenchymal state in comparison to epithelial state. Interestingly, inactive forms of PKC-theta and PKC-beta form complexes with LSD1 and Zeb1 on the chromatin template in epithelial cells. However, in mesenchymal cells, active PKC-theta switches its association to the active mark Pol II instead of LSD1 and Zeb1. Importantly, the data suggest that although phosphorylated PKC-theta is required for PKC-beta recruitment in the mesenchymal state, the two PKC isozymes, PKC-theta and PKC-beta play opposing roles in regulating transcription of inducible EMT genes. For the first time it has been shown that PKC-theta and PKC-beta tether to chromatin on the promoters of microRNA 200 family members during the process of the epithelial to mesenchymal transition. Not only does Pol II co-exist with PKC-theta in the mesenchymal state on the miR 200c promoter but, also, epigenetic tags such as LSD1 and Zeb-1 co-exist with Pol II in mesenchymal state, suggesting that ""Pol II capturing"" occurs in a PKC-theta containing repressive complex. Additionally, it was shown that PKC activity is important in controlling EMT and CSC formation by regulating EMT associated inducible genes and microRNAs. Collectively, the data presented in this thesis suggest that PKC isozymes might have ""dual role"" consisting of signal transduction role and chromatin associated role in controlling EMT and CSC formation processes. Furthermore, a previously undescribed layer of chromatin-tethered enzymes with interconnected function regulates transcription of EMT-associated inducible genes and microRNAs, include PKC isozymes, histone demethylases and DNA methyltransferases. -- provided by Candidate.