Дисертації з теми "HIPPO-PATHWAY-YAP"
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Bui, Duyen Amy. "The Hippo Pathway Effector YAP Regulates Cytokinesis." Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:17467231.
Повний текст джерелаMedical Sciences
Moleirinho, Susana. "Mammalian upstream Hippo signalling pathway proteins activate core pathway kinases and functionally antagonize oncogenic YAP." Thesis, University of St Andrews, 2013. http://hdl.handle.net/10023/3662.
Повний текст джерелаToloczko, Aleksandra. "Deubiquitination and control of the Hippo pathway." Thesis, University of Manchester, 2017. https://www.research.manchester.ac.uk/portal/en/theses/deubiquitination-and-control-of-the-hippo-pathway(8afdf3df-8635-4116-99c8-57fbe423501e).html.
Повний текст джерелаSidor, C. M. "Mask proteins are co-factors of Yorkie/YAP in the Hippo signaling pathway." Thesis, University College London (University of London), 2012. http://discovery.ucl.ac.uk/1352451/.
Повний текст джерелаAstone, Matteo. "A novel Yap/Taz zebrafish reporter reveals a role of Hippo pathway transducers in angiogenesis." Doctoral thesis, Università degli studi di Padova, 2015. http://hdl.handle.net/11577/3424650.
Повний текст джерелаYAP e TAZ, orchestrando la proliferazione, la morte e il differenziamento cellulari, rappresentano elementi chiave di una complessa rete di vie di segnalazione che agiscono durante lo sviluppo. L’alterazione della segnalazione YAP/TAZ causa una crescita fuori controllo degli organi durante l’organogenesi, che si traduce nella perdita dell’omeostasi tissutale nell’adulto e conseguente sviluppo tumorale. YAP/TAZ sono co-attivatori trascrizionali che interagiscono con i fattori di trascrizione TEAD per promuovere la proliferazione e la sopravvivenza cellulari. La loro attività trascrizionale è regolata dal trasporto nucleo-citoplasmatico e dall’accumulo nucleare, che sono controllati dalla cascata chinasica della via di Hippo, ma anche dagli stimoli meccanici percepiti dalla cellula e da altre vie. Fra queste, la via di Wnt/β-catenina assume una particolare rilevanza, dal momento che è stato recentemente dimostrato che essa regola l’attività di YAP/TAZ attraverso il loro sequestro nel complesso di degradazione della β-catenina mediato da AXIN. In questa tesi vengono descritte la generazione, la validazione e la caratterizzazione di un nuovo zebrafish biosensore che riporta l’attività di Yap/Taz. Esso esprime le proteine mCherry nucleare, eGFP o la proteina verde fluorescente destabilizzata VenusPEST sotto il controllo di un frammento promotoriale del gene umano CTGF target di YAP/TAZ, contenente 3 siti di legame per TEAD. Sono stati identificati diversi pesci fondatori indipendenti in grado di trasmettere il transgene alla linea germinale, i quali sono stati utilizzati per instaurare le linee reporter stabili. Tutti i pesci transgenici condividevano un pattern di espressione similare, mantenuto nelle generazioni successive. Per validare il reporter sono stati usati approcci di downregolazione e overespressione. La co-iniezione di due morfolini diretti contro i pre-mRNA di Yap e Taz ha ridotto il segnale reporter, mentre l’iniezione di mRNA codificanti per una forma costitutivamente attiva di Yap, Taz o Tead (YAP-5SA, TAZ-4SA, TEAD-VP16) lo ha aumentato. Le linee transgeniche basate sul gene CTGF rappresentano perciò bona fide dei reporter dell’attività di Yap/Taz. Durante lo sviluppo, un forte segnale reporter è visibile principalmente nella lente, la vescicola otica, gli archi faringei, il cuore, la pinna pettorale e la rete vascolare, ma l’espressione della proteina reporter è rilevabile in molti altri tessuti e organi. L’attivazione quasi ubiquitaria di Yap/Taz osservata durante l’embriogenesi precoce, consistente con il ruolo generale di YAP/TAZ nel promuovere la proliferazione cellulare e la crescita degli organi, è ampiamente silenziata nel pesce adulto, dove il segnale reporter è ristretto a lente, ovario, cuore e intera rete vascolare. Lo zebrafish biosensore è anche in grado di riportare l’attivazione di Yap/Taz durante la rigenerazione della coda nella larva e nell’adulto, come atteso dal ruolo che riveste la segnalazione YAP/TAZ nei processi rigenerativi. Lo zebrafish reporter basato sul gene CTGF ha permesso di mostrare in un organismo vivente durante lo sviluppo la regolazione che la via di Wnt/β-catenina esercita sull’attività di Yap/Taz. I nostri risultati in termini di variazione del segnale reporter, in seguito alla modulazione genetica e farmacologica dell’attività della via di Wnt, sono in linea con il modello disegnato di recente in vitro. L’attività generale e sostenuta del reporter nell’endotelio durante l’embriogenesi ha suggerito un coinvolgimento funzionale della segnalazione Yap/Taz nell’angiogenesi precoce. La downregolazione di Yap/Taz è risultata in una compromissione della crescita dei vasi intersegmentali (ISVs), mentre l’attivazione spinta della trascrizione mediata da Yap/Taz ha causato un ramificarsi anomalo degli ISVs. La capacità di Yap/Taz di promuovere tale ramificazione vascolare è “cell-autonomous”, dal momento che lo stesso fenomeno è stato osservato esprimendo TAZ-4SA sotto il controllo di un promotore endotelio-specifico. Lo zebrafish reporter sviluppato è un nuovo potente strumento per studiare in vivo l’attivazione della via di Yap/Taz, con possibili applicazioni nello screening farmacologico e nella biologia della rigenerazione e del cancro. Ha permesso di confermare in vivo durante lo sviluppo l’interazione fra le vie di Wnt/β-catenina e Yap/Taz e di scoprire un nuovo ruolo di Yap/Taz nella ramificazione vascolare, suggerendo una funzione pro-angiogenica dell’attività trascrizionale di YAP/TAZ.
Meléndez, García Rodrigo. "YAP as a Regulator of DNA Replication Timing." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASL014.
Повний текст джерелаStemness could be defined as a state in which a cell is able to self-renew and/or to differentiate after cell division. Before this happens, exhaustive duplication of the genome free of errors must occur in order to avoid deleterious mutations, a hallmark of cancer. Thus, DNA replication is particularly important to stem cells because of their continuous division capacities. Regarding DNA replication in eukaryotes, it was discovered that segments of chromosomes close in space, replicate in a coordinated manner during S phase, a process called replication timing. Moreover, major changes in replication timing correlate with cell differentiation, 3D chromatin architecture and transcription. However, the molecules that govern its regulation are poorly understood. Previously, my laboratory found that YAP, the downstream effector of the Hippo pathway, regulates S phase progression of retinal stem cells in Xenopus laevis. To test YAP function in the direct control of replication timing, we took advantage of the powerful in vitro DNA replication system of X. laevis egg extracts. Briefly, we discovered that YAP is recruited to replicating chromatin dependently of origin licensing. In addition, YAP depleted extracts showed increased DNA synthesis and origin activation; revealing that YAP normal function is to slow-down replication by limiting origin firing. Interestingly, we found Rif1, a major regulator of replication timing, as a novel partner of YAP. In vivo, Rif1 expression overlaps that of Yap within the stem cell compartment of the Xenopus retina. Knockdown of Rif1 leaded to a small-eye phenotype and alterations in replication foci of retinal stem cells, resembling the effect observed in YAP deficient cells. Finally, early-embryonic depletion of both molecules resulted in a strikingly acceleration of cell division.Altogether, our findings unveil YAP implication in the regulation of replication dynamis and show Rif1 as a novel partner. Further investigation to analyze this interaction would help us to understand the biological relevance in the control of replication timing and whether it could be used as a target in regenerative medicine
Cherrett, Claire. "Structural and functional studies of proteins from the Hippo signalling pathway." Thesis, University of Bath, 2011. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.548103.
Повний текст джерелаGarcía-García, Diana. "Müller Cells and Retinal Regeneration : The Role of the Hippo/YAP Signaling Pathway Yap Haploinsufficiency Leads to Müller Cell Dysfunction and Late-Onset Cone Dystrophy Linking YAP to Müller Glia Quiescence Exit in the Degenerative Retina." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASL068.
Повний текст джерелаDegenerative diseases of the retina are one of the main causes of blindness. Among the various therapeutic strategies currently being studied, our team is focusing on the regenerative potential of the retina. One cellular source of interest are Müller cells, the main type of glial cells in the retina capable of reactivating in case of degeneration, a process called reactive gliosis, and in some species adopting certain characteristics of stem cells. If such a process sustains powerful regeneration abilities in teleosts, it is however largely inefficient in mammals. Hence, increasing our knowledge of the molecular mechanisms underlying the behaviour of these cells under pathological conditions may help turning their regenerative properties into new therapeutic strategies. In this context, my laboratory focused on the terminal effector of the Hippo pathway, the co-transcriptional factor YAP, which has been shown to stimulate regeneration of several injured organs. In the retina, YAP is specifically expressed in Müller cells and upregulated in case of damage. However, its function in retinal homeostasis, and its role in retinal regeneration remained unknown.The first part of my PhD aimed at deciphering YAP function in mouse Müller cells in both physiological and pathological conditions. In essence, we revealed a central role of YAP in Müller cell-dependent retinal homeostasis and as such, as a key player for cone survival during aging. In case of retinal damage, we showed that YAP upregulation is critical for cell-cycle gene reactivation that normally accompanies reactive gliosis. In this context, we also found a functional interaction between YAP and the EGFR signaling pathway, supporting a function of YAP as a hub within the complex signaling network of key regenerative signaling pathways. I also found that YAP overactivation is sufficient to induce mouse Müller cell reprogramming into highly proliferative cells, mimicking a fish or amphibian condition, when Müller cells spontaneously proliferate upon injury. As a whole, this work highlights the critical role of YAP in driving mammalian Müller cells to exit quiescence and thus reveals a potential target for regenerative medicine.The second part of my PhD project stemmed from the emerging discoveries highlighting inflammatory pathways as regulators of the regenerative process. Although inflammation is considered to hamper retinal regeneration in mammals, there are no studies regarding the influence of inflammation on mouse Müller cell-dependent regenerative process. In addition, recent discoveries on the role of YAP in the regulation of the inflammatory process lead to the hypothesis that it could play a role in the relationship between inflammation and retinal regeneration. I thus aimed at investigating the role played by the injury-induced inflammation on mouse Müller cell behavior and how YAP fits in this interplay. I unexpectedly discovered that a microglial-dependent pro-inflammatory context stimulates mouse Müller cell proliferation in retinal explants. Importantly, my results showed that this mitogenic effect occurs in a YAP-dependent manner. Moreover, I uncovered that the effect of YAP overexpression on Müller cell proliferation can be potentiated by a pro-inflammatory environment, and abolished upon microglia depletion. Finally, we found that, in turn, YAP regulates key inflammatory cytokines. Altogether, this part of my project not only deepen our knowledge regarding the impact of inflammation on mouse Müller cell behavior, it also highlights YAP as a key player in the crosstalk between inflammation and retinal regeneration
Kimura, Masahiro. "Homeobox A4 Suppresses Vascular Remodeling as a Novel Regulator of YAP/TEAD Transcriptional Activity." Kyoto University, 2020. http://hdl.handle.net/2433/253486.
Повний текст джерелаRuggeri, Naomi. "REGULATION OF YAP BY GLUCOCORTICOIDS." Doctoral thesis, Università degli studi di Trieste, 2015. http://hdl.handle.net/10077/11122.
Повний текст джерелаThe Hippo signalling pathway is tumour suppressor cascade with a central role in the regulation of fundamental cellular biological processes, such as cell proliferation, apoptosis, organ size control and stem cell functions. The Hippo pathway transduces external signals that come to the cell into the nucleus, where it can control the expression of specific target genes, mainly involved in cell proliferation and differentiation. The Hippo pathway is an inhibitory pathway that control by phosphorylation and inhibition Yes-associated protein (YAP) coactivator, one of the two nuclear effectors of this signalling, involved in the regulation of proliferation and organ size. As consequence, deregulation of Hippo tumor suppressor pathway or hyperactivation of its downstream effectors is often associated with formation, development and tumour dissemination. Consistently, YAP is often over-expressed in a broad range of different tumours and it has aberrant activity in breast cancer as well as in several other human carcinomas. Up-regulation of YAP activity increases stem cell self-renewal in normal and cancer stem cells. In this work we describe the identification of a new hormonal-dependent layer for YAP regulation in breast cancer by the glucocorticoids and we analyze the mechanisms through which this regulation occurs. We found that Glucocorticoid Receptor (GR) binds directly the YAP promoter and induces the transcription of YAP mRNA after GC stimulation in cancer cells. Moreover, GC lead to efficient YAP de-phosphorylation and transcriptional activation, in a transcription-independent manner, by inducing actin cytoskeleton reorganization. Importantly, inhibition of the GR by means of RU486 (GR competitive antagonist) strongly blunted the expansion of the cancer stem cell pool in breast cancer cells by blunting the GR/YAP axis.
XXVII Ciclo
1987
Hamon, Annaïg. "Etude de la signalisation Hippo/YAP dans les cellules gliales de Müller en conditions physiologiques et pathologiques de dégénérescence rétinienne chez la souris." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS558/document.
Повний текст джерелаRetinal dystrophies are one of the main causes of blindness. Among the different therapeutic strategies currently studied, our team is interested in the regenerative potential of endogenous retinal cells. A cellular source of interest are Müller cells, which are the main type of glial cells in the retina. These cells are able to reactivate in case of retinal degeneration and adopt various characteristics of stem cells. They enter a state called reactive gliosis. While in some species such as the fish, they allow the complete regeneration of the retina, they have very limited and ineffective regenerative capacities in mammals. Increasing our knowledge of the complex molecular response of Müller cells to retinal degeneration is thus essential for the development of promising new therapeutic strategies. In this context, the aim of my thesis project was to study the role of the co-transcription factor YAP in Müller cells reactivation. This protein is the main effector of the Hippo signaling pathway which is a crucial player in the field of stem cell biology and regeneration.As a first step, we performed a transcriptomic analysis, which revealed that the Hippo/YAP pathway is one of the main signaling deregulated in a mouse model of photoreceptor degeneration. In particular, we found that YAP is specifically expressed in Müller cells and strongly upregulated upon retinal degeneration, when these cells are reactivated. We thus uncovered for the first time a link between the Hippo/YAP pathway and reactive gliosis in the retina. Consequently, the second part of my thesis project was to undertake a functional study of YAP in Müller cells. For this purpose, we generated, by crossing, a mouse model allowing for Yap conditional knockout specifically in these cells. This model allowed us to show that Yap deletion leads to deregulation of several Müller cell specific genes. A phenotypic analysis revealed that these molecular deregulations lead to premature aging of Müller cells and visual defects in old mice. These results suggest that YAP is required for normal function of Müller glial cells. We then studied the impact of Yap deletion in Müller cells under degenerative conditions. A transcriptomic analysis revealed that various aspects of the molecular response of reactive Müller cells are affected in the absence of Yap. Among the deregulated biological processes, we focussed in particular in the regulation of cell proliferation. We found that YAP is required to trigger cell cycle gene upregulation that occurs in Müller glial cells following photoreceptor cell death. Furthermore, our results suggest that some components of the EGFR signaling pathway, which is known for its central role in the reactivation of Müller cells in pathological conditions, are regulated by YAP in Müller cells.Taken together, these results highlight the importance of YAP (i) in Müller cell function under physiological conditions to maintain retinal homeostasis, and (ii) in the regulation of Müller cell reactivation process under degenerative conditions. Moreover, these data allow us to propose a model in which YAP would be involved in the control of Müller glia cell cycle re-entry through its interaction with the EGFR signaling pathway. Therefore, this work has contributed to increase our knowledge of the signaling network involved in the reactivation of Müller cells in the mammalian retina
Hamze, komaiha Ola. "Etude de la polarité apico-basale dans les cellules épithéliales et son implication dans le cholangiocarcinome intrahépatique : contribution de l'inositol 5-phosphatase SHIP2." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS014.
Повний текст джерелаCell polarity is critical caracteristic for the maintenance of tissue architecture. Cell division, ciliogenesis, cell proliferation and migration are events tightly associated to cell polarization processes. Alteration in cell polarity contributes to loss of epithelium integrity and enhances cancer development. Lipids signaling, such as phosphatidylinositol (PtdIns), play a vital role in apico-basal polarity. In this study, we developed researches to better understand mechanisms implicated the role of the phosphatase SHIP2 in cell polarity. We demonstrated that SHIP2 is implicated in formation of the apical membrane initiation site (AMIS) by regulating YAP, a component of Hippo pathway, and RhoA-dependant acto-myosin contractility. Furthermore, we demonstrated that inhibition of SHIP2 contributes to defect in the formation and cleavage of the mitotic spindle. Overexpression of SHIP2 induced a large lumen with long cilia due to a decrease in YAP, Aurora A and HEF1 luminal localization. On the contrary, down regulation of SHIP2 impaired cilia outgrowth by increasing Aurora A, HEF1 and YAP luminal localization with appearance of a multilumens phenotype. Thus, our results reinforced the role of SHIP2 in maintain of integrity and homeostasis of epithelial cells. In this study, we also demonstrated that expression of SHIP2 distinguished the different types of liver cancer (HCC, ICC and mixte), and that SHIP2 and Merlin/NF2 are overexpressed in ICC which is the opposite of YAP and RhoA expression
Poirson, Juline. "Interactome des oncoprotéines E6 et E7 des HPV : du système ubiquitine-protéasome à la voie de signalisation Hippo." Thesis, Strasbourg, 2016. http://www.theses.fr/2016STRAJ052.
Повний текст джерелаThe human papillomavirus (HPVs) are the archetype of DNA oncogenic viruses. High-risk mucosal HPVs (mainly HPV16) are the main causative agents of cervical cancer and are also involved in other cancers. HPV oncogenic properties are mainly due to the expression of E6 and E7 proteins. We built a resource composed of 600 cDNA encoding the human ubiquitin-proteasome system (UPS) effectors and identified novel E6 and E7 potential targets by using a method based on the complementation of the Gaussia princeps luciferase (GPCA). HPV16 E6 binds to specific LxxLL motifs present in E6AP and IRF3. We have solved the crystallographic structure of the E6/E6AP LxxLL/p53 and E6/IRF3 LxxLL complexes. Furthermore, HPV may target a novel tumour suppressor pathway, the Hippo signalling pathway with its two main mediators YAP and TAZ. We have built a cDNA library dedicated to the 265 human PDZ domains and identified news potential partners of YAP and TAZ proteins by using the GPCA. The results provide novel insights on HPV biology and their oncogenic property
Dutta, Shubham. "Role of TRIP6 and Angiomotins in the Regulation of the Hippo Signaling Pathway." eScholarship@UMMS, 2018. https://escholarship.umassmed.edu/gsbs_diss/964.
Повний текст джерелаCROCI, OTTAVIO. "GENOMIC LANDSCAPE AND TRANSCRIPTIONAL REGULATION BY YAP AND MYC IN THE LIVER." Doctoral thesis, Università degli Studi di Milano, 2018. http://hdl.handle.net/2434/556194.
Повний текст джерелаSorrentino, Giovanni. "Metabolic control of YAP/TAZ by the Mevalonate Pathway." Doctoral thesis, Università degli studi di Trieste, 2014. http://hdl.handle.net/10077/10119.
Повний текст джерелаThe YAP and TAZ mediators of the Hippo pathway (hereafter called YAP/TAZ) promote tissue proliferation and organ growth. However, how their biological properties intersect with cellular metabolism remains unexplained. Here, we show that YAP/TAZ activity is controlled by the SREBP/mevalonate pathway. Inhibition of the rate-limiting enzyme of this pathway (HMG-CoA reductase) by statins opposes YAP/TAZ nuclear localization and transcriptional responses. Mechanistically, the geranylgeranyl pyrophosphate produced by the mevalonate cascade is required for activation of Rho GTPases that, in turn, activate YAP/TAZ by inhibiting their phosphorylation and promoting their nuclear accumulation. The mevalonate–YAP/TAZ axis is required for proliferation and self-renewal of breast cancer cells. In Drosophila melanogaster, inhibition of mevalonate biosynthesis and geranylgeranylation blunts the eye overgrowth induced by Yorkie, the YAP/TAZ orthologue. In tumour cells, YAP/TAZ activation is promoted by increased levels of mevalonic acid produced by SREBP transcriptional activity, which is induced by its oncogenic cofactor mutant p53. These findings reveal an additional layer of YAP/TAZ regulation by metabolic cues.
XXVI Ciclo
1983
Hiemer, Samantha Elizabeth. "Defining mechanisms directing YAP/TAZ-mediated tumorigenesis." Thesis, 2016. https://hdl.handle.net/2144/14589.
Повний текст джерелаKhaliqdina, Shoheera. "YAP-regulated epithelial-fibroblast crosstalk." Thesis, 2015. https://hdl.handle.net/2144/16285.
Повний текст джерелаThompson, Abigail Fisk. "Identification of Novel Small Molecule Inhibitors of YAP-TEAD Binding within the Hippo Signaling Pathway." Thesis, 2020. http://hdl.handle.net/1805/24084.
Повний текст джерелаThe Hippo signaling pathway controls organ size by regulating cell proliferation, apoptosis, and cell differentiation. The Hippo pathway ultimately regulates the concentration of the coactivator yes-associated protein 1 (YAP1) in the nucleus, which binds the transcription factor TEA domains (TEAD), activating genes related to cell proliferation. In several cancers, increased YAP1 activity is linked to increased cellular proliferation, de-differentiation and survival to drive tumor progression and spreading. The development of inhibitors against YAP-TEAD binding are consequently a research topic of much interest. While several inhibitors of the YAP-TEAD interaction are reported, none possess both high specificity and anti-tumor activity. The work described here is based upon a collaboration with AtomWise, Inc to find a best in class competitive inhibitor of YAP-TEAD binding. AtomWise completed a computational screen of ten million compounds for potential binding to a TEAD pocket that is essential for interaction with YAP1. This master’s thesis encompasses both intracellular and biochemical validation of these compounds. Initially, a luciferase YAP/TEAD dependent reporter assay was used to identify compounds with potential intracellular activity. This data was compared with the action of these compounds on the metabolic activity (MTT assay) across three cancer cell lines. Three sulfonamide-based compounds, 4, 22, and 59 were identified as top 10 YAP/TEAD inhibitors. Six additional compounds were synthesized that combined specific moieties in these three compounds. Dose response curves for inhibition of TEAD reporter activity showed that compounds 22 and 59 exhibited both high inhibition and low IC50 values relative to the derivatives. Further, compound 22 also significantly reduced the levels of CTGF transcript (measured by RT-qPCR), a surrogate measure for endogenous YAP1: TEAD activity. Preliminary fluorescent polarization data also suggests that compound 22 inhibits the binding of a 5(6)-FAM labeled YAP1 peptide (residues 58-74) to a purified TEAD fragment. In this work, compounds 22 and 59 are found to inhibit TEAD dependent transcription and the growth of multiple cancer cell lines. In addition, promising preliminary biochemical data indicates that compound 22 may inhibit the interaction of YAP1 with TEAD.
Θεοδωροπούλου, Ανδριάνα. "Μελέτη της έκφρασης σηματοδοτικών μορίων που εμπλέκονται στη βιολογική συμπεριφορά των μηνιγγιωμάτων του ανθρώπου". Thesis, 2012. http://hdl.handle.net/10889/5448.
Повний текст джерелаMeningiomas are among the most common primary tumors of the Central Nervous System, but relatively understudied. The majority of meningiomas are benign tumors (WHO grade I), but almost 10% of all diagnosed meningiomas exhibit malignant features, such as invasiveness to the surrounding brain tissue, high recurrence rate, etc. Hippo signaling pathway is an evolutionary highly conserved protein kinase cascade involved in organ size control, cell proliferation and apoptosis, differentiation and cancer development. Very few are known about the role of Hippo pathway and meningiomas. In this study we attempt to find out whether Hippo path functions differently between high and low grade meningiomas. For this purpose paraffin embedded tissues obtained from 53 patients who underwent surgical removal of meningiomas were examined histoimmunologicaly. 34 out of 53 cases were low grade meningiomas and 19 out of 53 were high grade meningiomas. The paraffin sections were immunostained with CD44, YAP and TAZ antibodies, components of the Hippo signaling pathway. We observed statistically significant association between the expression of CD44, YAP and TAZ. There was a significant correlation between high grade meningiomas and expression of the examined factors. Moreover there was a significant difference in nuclear accumulation of YAP and TAZ between high and low grade meningiomas. Our findings suggest that in high grade meningiomas, Hippo pathway is inactivated and YAP and TAZ transcriptional co activators are able to insert nucleus and promote proliferation and antiapoptosis. This may be due to CD44 function, which interacts with merlin, an upstream regulator of the Hippo path. More experiments are required to verify the exact mechanism.
Bolgioni-Smith, Amanda. "Defining the roles of YAP/TAZ in controlling cell fate decisions following abnormal mitosis." Thesis, 2018. https://hdl.handle.net/2144/32960.
Повний текст джерела2020-10-24T00:00:00Z
St-Jean, Guillaume. "Élucidation des rôles des voies Wnt et Hippo dans le développement et la fonction du tractus reproducteur femelle chez la souris." Thesis, 2019. http://hdl.handle.net/1866/24240.
Повний текст джерелаThe development of the female reproductive tract arises from the coordination of numerous signaling pathways regulating processes such as proliferation, differentiation and apoptosis during embryogenesis. The Wnt and Hippo pathways are known to be involved in these processes. Wnt pathway activation, via its specific ligands, results in the stabilisation and increased transcriptional activity of β-catenin. The Hippo pathway does not possess any specific ligands. In contrast to Wnt, inactivation of the Hippo pathway (via Lats1 and Lats2 kinases) is required for the stabilization and increased activity of the transcriptional coactivators YAP and TAZ. The Wnt pathway is known to be involved in the development of the female reproductive tract. Further evidence also suggests the possibility of functional redundancy amongst certain WNT ligands such as Wnt4 and Wnt5a. The Hippo pathway is not known to be implicated in the development of the female reproductive tract. However, numerous interactions have been reported between both pathways, suggesting a possible unknown role of Hippo in that context. The objective of this project was to elucidate the roles of Wnt4, Wnt5a, Lats1 and Lats2 in the Müllerian mesenchyme and the development of the uterus. Results from our first study confirmed the partially redundant roles of Wnt4 and Wnt5a in the development of the uterus. Our model was notably characterized by developmental abnormalities and loss of uterine functions resulting in in vivo decidualization defects and loss of conceptus viability. Results from our second study confirmed the redundant roles of Lats1 and Lats2 in the maintenance of Müllerian mesenchymal cell multipotency. We observed premature differentiation of Müllerian mesenchymal cells into myofibroblasts in absence of both Lats1 and Lats2. These changes were in part due to the increased expression of the target gene Ctgf. Our additional results could not demonstrate any potential interactions between the Wnt and Hippo pathways that could explain the phenotypic changes. In conclusion, our studies confirmed and further discovered novel roles of these pathways in the development of the Müllerian ducts. These models could also lead to better understanding of the pathophysiology of certain uterine diseases and the discovery of potential therapeutic approaches.
Tsoi, Mayra. "Élucidation du rôle de la voie Hippo dans l’ovaire chez la souris." Thèse, 2018. http://hdl.handle.net/1866/21070.
Повний текст джерелаMueller, Kaly Alyse. "The Hippo pathway in liver regeneration and tumorigenesis." Thesis, 2014. https://hdl.handle.net/2144/14680.
Повний текст джерела