Journal articles: 'Cancer transcription'

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Otálora-Otálora, Beatriz Andrea, Liliana López-Kleine, and Adriana Rojas. "Lung Cancer Gene Regulatory Network of Transcription Factors Related to the Hallmarks of Cancer." Current Issues in Molecular Biology 45, no. 1 (January 5, 2023): 434–64. http://dx.doi.org/10.3390/cimb45010029.

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The transcriptomic analysis of microarray and RNA-Seq datasets followed our own bioinformatic pipeline to identify a transcriptional regulatory network of lung cancer. Twenty-six transcription factors are dysregulated and co-expressed in most of the lung cancer and pulmonary arterial hypertension datasets, which makes them the most frequently dysregulated transcription factors. Co-expression, gene regulatory, coregulatory, and transcriptional regulatory networks, along with fibration symmetries, were constructed to identify common connection patterns, alignments, main regulators, and target genes in order to analyze transcription factor complex formation, as well as its synchronized co-expression patterns in every type of lung cancer. The regulatory function of the most frequently dysregulated transcription factors over lung cancer deregulated genes was validated with ChEA3 enrichment analysis. A Kaplan–Meier plotter analysis linked the dysregulation of the top transcription factors with lung cancer patients' survival. Our results indicate that lung cancer has unique and common deregulated genes and transcription factors with pulmonary arterial hypertension, co-expressed and regulated in a coordinated and cooperative manner by the transcriptional regulatory network that might be associated with critical biological processes and signaling pathways related to the acquisition of the hallmarks of cancer, making them potentially relevant tumor biomarkers for lung cancer early diagnosis and targets for the development of personalized therapies against lung cancer.

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Chen, Chia-Chun, Kai Song, Wendy Tran, Matthew Obusan, Tyler Sugimoto, Katherine Sheu, Donghui Cheng, et al. "Abstract 789: Elucidating transcriptional dynamics in neuroendocrine differentiation of advanced prostate cancer." Cancer Research 82, no. 12_Supplement (June 15, 2022): 789. http://dx.doi.org/10.1158/1538-7445.am2022-789.

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Abstract Small cell carcinomas of the lung, bladder, and prostate share similar transcription patterns and drug sensitivities. Due to their high cellular plasticity, these cancers often escape treatment through a trans-differentiation from adenocarcinoma to the neuroendocrine state. We previously developed a pan small cell cancer in vitro/in vivo model named PARCB that can recapitulate this transition from primary patient tissues. To understand which transcription factors may be important in this transition, we conducted bulk and single cell RNA sequencing over time. We identified a developmental trajectory that is shared among all samples and is defined by stage-specific transcription factors. We plan to interrogate the role that these transcription factors play in the PARCB transformation assay. We performed ATAC sequencing to investigate how these transcription factors regulate these transitional states. Our study will provide a basic understanding of the transcriptional changes that occur during neuroendocrine differentiation and provide new potential therapeutic targets for small cell cancers. Citation Format: Chia-Chun Chen, Kai Song, Wendy Tran, Matthew Obusan, Tyler Sugimoto, Katherine Sheu, Donghui Cheng, Grigor Varuzhanyan, Liang Wang, Lisa Ta, Zhiyuan Mao, Nathanael Bangayan, Jung-Wook Park, Thomas Graerber, Owen Witte. Elucidating transcriptional dynamics in neuroendocrine differentiation of advanced prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 789.

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Tsai, Jessica W., Paloma Cejas, Dayle K. Wang, Smruti Patel, David W. Wu, Phonepasong Arounleut, Xin Wei, et al. "FOXR2 Is an Epigenetically Regulated Pan-Cancer Oncogene That Activates ETS Transcriptional Circuits." Cancer Research 82, no. 17 (July 8, 2022): 2980–3001. http://dx.doi.org/10.1158/0008-5472.can-22-0671.

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Abstract Forkhead box R2 (FOXR2) is a forkhead transcription factor located on the X chromosome whose expression is normally restricted to the testis. In this study, we performed a pan-cancer analysis of FOXR2 activation across more than 10,000 adult and pediatric cancer samples and found FOXR2 to be aberrantly upregulated in 70% of all cancer types and 8% of all individual tumors. The majority of tumors (78%) aberrantly expressed FOXR2 through a previously undescribed epigenetic mechanism that involves hypomethylation of a novel promoter, which was functionally validated as necessary for FOXR2 expression and proliferation in FOXR2-expressing cancer cells. FOXR2 promoted tumor growth across multiple cancer lineages and co-opted ETS family transcription circuits across cancers. Taken together, this study identifies FOXR2 as a potent and ubiquitous oncogene that is epigenetically activated across the majority of human cancers. The identification of hijacking of ETS transcription circuits by FOXR2 extends the mechanisms known to active ETS transcription factors and highlights how transcription factor families cooperate to enhance tumorigenesis. Significance: This work identifies a novel promoter that drives aberrant FOXR2 expression and delineates FOXR2 as a pan-cancer oncogene that specifically activates ETS transcriptional circuits across human cancers. See related commentary by Liu and Northcott, p. 2977

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Rosado-Tristani, Diego A., Carlos S. Morales, Esther A. Peterson, and Jose A. Rodríguez-Martínez. "Abstract 2275: Transcription factor landscape cataloguing highlights key insights in inflammatory breast cancer (IBC)." Cancer Research 82, no. 12_Supplement (June 15, 2022): 2275. http://dx.doi.org/10.1158/1538-7445.am2022-2275.

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Abstract Transcription factors are proteins that bind to DNA in a sequence-specific manner to regulate gene expression for normal cellular functions. Cancers have been shown to have aberrant transcriptional regulation. Therefore, identifying transcription factor landscapes will aid in characterizing complex diseases. As an example, breast cancer has many subtypes that are phenotypically and molecularly distinct. Inflammatory Breast Cancer (IBC) is rare, and the most aggressive form of breast cancer currently known. It is a poorly characterized subtype, and diagnosis often results in poor prognosis for patients. As such, we decided to explore the transcription factor landscape in IBC. This was accomplished employing the following strategy: 1) We assembled de novo transcriptomes for SUM149, an IBC cancer line and MCF7, a non-IBC cancer line using Trinity; 2) We translated the assembled transcriptomes using getORF from EMBOSS; 3) We identified putative transcription factors in the translated transcriptomes using CREPE. We then identified differentially expressed genes between SUM-149 and MCF-7 using DEseq2. Our results highlight differences in the transcription factor catalogues between IBC and non-IBC cancers. Of interest in SUM-149 is the gene BNC1, a member of the C2H2 zinc finger family of transcription factors. Dysregulation of this gene is associated with brain metastasis in breast cancers which is a common phenotype in IBC. BNC1-associated genes are linked to GO terms such as, epithelial cell differentiation, and regulation of alternative mRNA splicing, via spliceosome; however, BNC1 functions in IBC are yet to be determined. This analysis will bridge the gap in knowledge of key transcriptional regulators in IBC. Citation Format: Diego A. Rosado-Tristani, Carlos S. Morales, Esther A. Peterson, Jose A. Rodríguez-Martínez. Transcription factor landscape cataloguing highlights key insights in inflammatory breast cancer (IBC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2275.

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Ishihara, Seiichiro, and Hisashi Haga. "Matrix Stiffness Contributes to Cancer Progression by Regulating Transcription Factors." Cancers 14, no. 4 (February 18, 2022): 1049. http://dx.doi.org/10.3390/cancers14041049.

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Matrix stiffness is critical for the progression of various types of cancers. In solid cancers such as mammary and pancreatic cancers, tumors often contain abnormally stiff tissues, mainly caused by stiff extracellular matrices due to accumulation, contraction, and crosslinking. Stiff extracellular matrices trigger mechanotransduction, the conversion of mechanical cues such as stiffness of the matrix to biochemical signaling in the cells, and as a result determine the cellular phenotypes of cancer and stromal cells in tumors. Transcription factors are key molecules for these processes, as they respond to matrix stiffness and are crucial for cellular behaviors. The Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) is one of the most studied transcription factors that is regulated by matrix stiffness. The YAP/TAZ are activated by a stiff matrix and promotes malignant phenotypes in cancer and stromal cells, including cancer-associated fibroblasts. In addition, other transcription factors such as β-catenin and nuclear factor kappa B (NF-κB) also play key roles in mechanotransduction in cancer tissues. In this review, the mechanisms of stiffening cancer tissues are introduced, and the transcription factors regulated by matrix stiffness in cancer and stromal cells and their roles in cancer progression are shown.

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Cox, PM, and CR Goding. "Transcription and cancer." British Journal of Cancer 63, no. 5 (May 1991): 651–62. http://dx.doi.org/10.1038/bjc.1991.151.

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Arancio, Walter, and Claudia Coronnello. "Repetitive Sequence Transcription in Breast Cancer." Cells 11, no. 16 (August 14, 2022): 2522. http://dx.doi.org/10.3390/cells11162522.

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Repetitive sequences represent about half of the human genome. They are actively transcribed and play a role during development and in epigenetic regulation. The altered activity of repetitive sequences can lead to genomic instability and they can contribute to the establishment or the progression of degenerative diseases and cancer transformation. In this work, we analyzed the expression profiles of DNA repetitive sequences in the breast cancer specimens of the HMUCC cohort. Satellite expression is generally upregulated in breast cancers, with specific families upregulated per histotype: in HER2-enriched cancers, they are the human satellite II (HSATII), in luminal A and B, they are part of the ALR family and in triple-negative, they are part of SAR and GSAT families, together with a perturbation in the transcription from endogenous retroviruses and their LTR sequences. We report that the background expression of repetitive sequences in healthy tissues of cancer patients differs from the tissues of non-cancerous controls. To conclude, peculiar patterns of expression of repetitive sequences are reported in each specimen, especially in the case of transcripts arising from satellite repeats.

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Lai, Trang Huyen, Mahmoud Ahmed, Jin Seok Hwang, Sahib Zada, Trang Minh Pham, Omar Elashkar, and Deok Ryong Kim. "Transcriptional Repression of Raf Kinase Inhibitory Protein Gene by Metadherin during Cancer Progression." International Journal of Molecular Sciences 22, no. 6 (March 17, 2021): 3052. http://dx.doi.org/10.3390/ijms22063052.

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Raf kinase inhibitory protein (RKIP), also known as a phosphatidylethanolamine-binding protein 1 (PEBP1), functions as a tumor suppressor and regulates several signaling pathways, including ERK and NF-κκB. RKIP is severely downregulated in human malignant cancers, indicating a functional association with cancer metastasis and poor prognosis. The transcription regulation of RKIP gene in human cancers is not well understood. In this study, we suggested a possible transcription mechanism for the regulation of RKIP in human cancer cells. We found that Metadherin (MTDH) significantly repressed the transcriptional activity of RKIP gene. An analysis of publicly available datasets showed that the knockdown of MTDH in breast and endometrial cancer cell lines induced the expression RKIP. In addition, the results obtained from qRT-PCR and ChIP analyses showed that MTDH considerably inhibited RKIP expression. In addition, the RKIP transcript levels in MTDH-knockdown or MTDH-overexpressing MCF-7 cells were likely correlated to the protein levels, suggesting that MTDH regulates RKIP expression. In conclusion, we suggest that MTDH is a novel factor that controls the RKIP transcription, which is essential for cancer progression.

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Moparthi, Lavanya, Giulia Pizzolato, and Stefan Koch. "Wnt activator FOXB2 drives the neuroendocrine differentiation of prostate cancer." Proceedings of the National Academy of Sciences 116, no. 44 (October 14, 2019): 22189–95. http://dx.doi.org/10.1073/pnas.1906484116.

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The Wnt signaling pathway is of paramount importance for development and disease. However, the tissue-specific regulation of Wnt pathway activity remains incompletely understood. Here we identify FOXB2, an uncharacterized forkhead box family transcription factor, as a potent activator of Wnt signaling in normal and cancer cells. Mechanistically, FOXB2 induces multiple Wnt ligands, including WNT7B, which increases TCF/LEF-dependent transcription without activating Wnt coreceptor LRP6 or β-catenin. Proximity ligation and functional complementation assays identified several transcription regulators, including YY1, JUN, and DDX5, as cofactors required for FOXB2-dependent pathway activation. Although FOXB2 expression is limited in adults, it is induced in select cancers, particularly advanced prostate cancer. RNA-seq data analysis suggests that FOXB2/WNT7B expression in prostate cancer is associated with a transcriptional program that favors neuronal differentiation and decreases recurrence-free survival. Consistently, FOXB2 controls Wnt signaling and neuroendocrine differentiation of prostate cancer cell lines. Our results suggest that FOXB2 is a tissue-specific Wnt activator that promotes the malignant transformation of prostate cancer.

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Barrera, Giuseppina, Marie Angele Cucci, Margherita Grattarola, Chiara Dianzani, Giuliana Muzio, and Stefania Pizzimenti. "Control of Oxidative Stress in Cancer Chemoresistance: Spotlight on Nrf2 Role." Antioxidants 10, no. 4 (March 25, 2021): 510. http://dx.doi.org/10.3390/antiox10040510.

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Chemoresistance represents the main obstacle to cancer treatment with both conventional and targeted therapy. Beyond specific molecular alterations, which can lead to targeted therapy, metabolic remodeling, including the control of redox status, plays an important role in cancer cell survival following therapy. Although cancer cells generally have a high basal reactive oxygen species (ROS) level, which makes them more susceptible than normal cells to a further increase of ROS, chemoresistant cancer cells become highly adapted to intrinsic or drug-induced oxidative stress by upregulating their antioxidant systems. The antioxidant response is principally mediated by the transcription factor Nrf2, which has been considered the master regulator of antioxidant and cytoprotective genes. Nrf2 expression is often increased in several types of chemoresistant cancer cells, and its expression is mediated by diverse mechanisms. In addition to Nrf2, other transcription factors and transcriptional coactivators can participate to maintain the high antioxidant levels in chemo and radio-resistant cancer cells. The control of expression and function of these molecules has been recently deepened to identify which of these could be used as a new therapeutic target in the treatment of tumors resistant to conventional therapy. In this review, we report the more recent advances in the study of Nrf2 regulation in chemoresistant cancers and the role played by other transcription factors and transcriptional coactivators in the control of antioxidant responses in chemoresistant cancer cells.

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Wilanowski, Tomasz, and Sebastian Dworkin. "Transcription Factors in Cancer." International Journal of Molecular Sciences 23, no. 8 (April 18, 2022): 4434. http://dx.doi.org/10.3390/ijms23084434.

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Pandolfi, Pier Paolo. "Transcription therapy for cancer." Oncogene 20, no. 24 (May 2001): 3116–27. http://dx.doi.org/10.1038/sj.onc.1204299.

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Seth, Arun. "Transcription factors in cancer." European Journal of Cancer 41, no. 16 (November 2005): 2379–80. http://dx.doi.org/10.1016/j.ejca.2005.09.005.

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Shiah, Jamie V., Daniel E. Johnson, and Jennifer R. Grandis. "Transcription Factors and Cancer." Cancer Journal 29, no. 1 (January 2023): 38–46. http://dx.doi.org/10.1097/ppo.0000000000000639.

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Pecorari, Rosalba, Francesca Bernassola, Gerry Melino, and Eleonora Candi. "Distinct interactors define the p63 transcriptional signature in epithelial development or cancer." Biochemical Journal 479, no. 12 (June 24, 2022): 1375–92. http://dx.doi.org/10.1042/bcj20210737.

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The TP63 is an indispensable transcription factor for development and homeostasis of epithelia and its derived glandular tissue. It is also involved in female germline cell quality control, muscle and thymus development. It is expressed as multiple isoforms transcribed by two independent promoters, in addition to alternative splicing occurring at the mRNA 3′-UTR. Expression of the TP63 gene, specifically the amino-deleted p63 isoform, ΔNp63, is required to regulate numerous biological activities, including lineage specification, self-renewal capacity of epithelial stem cells, proliferation/expansion of basal keratinocytes, differentiation of stratified epithelia. In cancer, ΔNp63 is implicated in squamous cancers pathogenesis of different origin including skin, head and neck and lung and in sustaining self-renewal of cancer stem cells. How this transcription factor can control such a diverse set of biological pathways is central to the understanding of the molecular mechanisms through which p63 acquires oncogenic activity, profoundly changing its down-stream transcriptional signature. Here, we highlight how different proteins interacting with p63 allow it to regulate the transcription of several central genes. The interacting proteins include transcription factors/regulators, epigenetic modifiers, and post-transcriptional modifiers. Moreover, as p63 depends on its interactome, we discuss the hypothesis to target the protein interactors to directly affect p63 oncogenic activities and p63-related diseases.

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Blundon, Malachi A., and Subhamoy Dasgupta. "Metabolic Dysregulation Controls Endocrine Therapy–Resistant Cancer Recurrence and Metastasis." Endocrinology 160, no. 8 (June 3, 2019): 1811–20. http://dx.doi.org/10.1210/en.2019-00097.

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Abstract Cancer recurrence and metastasis involves many biological interactions, such as genetic, transcription, environmental, endocrine signaling, and metabolism. These interactions add a complex understanding of cancer recurrence and metastatic progression, delaying the advancement in therapeutic opportunities. We highlight the recent advances on the molecular complexities of endocrine-related cancers, focusing on breast and prostate cancer, and briefly review how endocrine signaling and metabolic programs can influence transcriptional complexes for metastasis competence. Nuclear receptors and transcriptional coregulators function as molecular nodes for the crosstalk between endocrine signaling and metabolism that alter downstream gene expression important for tumor progression and metastasis. This exciting regulatory axis may provide insights to the development of cancer therapeutics important for these desensitized endocrine-dependent cancers.

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Zhang, Gaihua, Yongbing Zhao, Yi Liu, Li-Pin Kao, Xiao Wang, Benjamin Skerry, and Zhaoyu Li. "FOXA1 defines cancer cell specificity." Science Advances 2, no. 3 (March 2016): e1501473. http://dx.doi.org/10.1126/sciadv.1501473.

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A transcription factor functions differentially and/or identically in multiple cell types. However, the mechanism for cell-specific regulation of a transcription factor remains to be elucidated. We address how a single transcription factor, forkhead box protein A1 (FOXA1), forms cell-specific genomic signatures and differentially regulates gene expression in four human cancer cell lines (HepG2, LNCaP, MCF7, and T47D). FOXA1 is a pioneer transcription factor in organogenesis and cancer progression. Genomewide mapping of FOXA1 by chromatin immunoprecipitation sequencing annotates that target genes associated with FOXA1 binding are mostly common to these cancer cells. However, most of the functional FOXA1 target genes are specific to each cancer cell type. Further investigations using CRISPR-Cas9 genome editing technology indicate that cell-specific FOXA1 regulation is attributable to unique FOXA1 binding, genetic variations, and/or potential epigenetic regulation. Thus, FOXA1 controls the specificity of cancer cell types. We raise a “flower-blooming” hypothesis for cell-specific transcriptional regulation based on these observations.

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Doak, Andrea E., Rose Qu, and Kevin J. Cheung. "Abstract A014: Transcriptional regulation of basal leader cell identity during collective breast cancer invasion." Cancer Research 83, no. 2_Supplement_2 (January 15, 2023): A014. http://dx.doi.org/10.1158/1538-7445.metastasis22-a014.

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Abstract An early step in breast cancer progression is invasion of tumor cells into surrounding tissues. In many breast cancers, particularly ductal carcinomas, this invasion is accomplished by tumor cells migrating as a cohesive group. This often involves cells that take on heterogeneous roles as either leader or follower cells. Studies in common mouse and human breast cancer models have established that leader cells express high levels of keratin-14 (K14) and other basal epithelial markers. The presence of these K14+ cells promote metastasis and predict poor prognosis. The molecular mechanisms regulating K14+ leader cell identity and the methods for targeted depletion of these cells remain obscure. Here we performed time-sampled single cell RNA-sequencing in 3D type I collagen-embedded tumor organoids isolated from the MMTV-PyMT luminal B model of breast cancer. 11 distinct cellular transcriptional states were identified, and through correlation with K14 expression and invasive strand formation we classified one of the states as leader cells. Having confirmed the leader cell cluster markers spatially localize to the invasive front, we next asked which transcription factors were enriched, reasoning that transcription factors could be master regulators of leader cell fate. Three different shRNAs targeting ten genes were systematically evaluated for their effects on collective invasion and keratin-14 transcription. Each transcription factor was designated as either an invasion promoter or invasion suppressor depending on the correlation between transcription factor expression and organoid invasion. Studies are ongoing investigating the impact of invasion-promoting and invasion-suppressing transcription factors on cellular transcriptional states and metastatic dissemination in-vivo. We propose that targeting invasion-suppressing pathways could be combined with therapies that specifically target and eliminate K14+ invasive cells. To this end, we have identified multiple candidate druggable targets and specific surface markers expressed in K14+ invasive cells. Citation Format: Andrea E. Doak, Rose Qu, Kevin J. Cheung. Transcriptional regulation of basal leader cell identity during collective breast cancer invasion [abstract]. In: Proceedings of the AACR Special Conference: Cancer Metastasis; 2022 Nov 14-17; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_2):Abstract nr A014.

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Penzo, Arnoldo, Pegoraro, Petrosino, Ros, Zanin, Wiśniewski, Manfioletti, and Sgarra. "HMGA1 Modulates Gene Transcription Sustaining a Tumor Signalling Pathway Acting on the Epigenetic Status of Triple-Negative Breast Cancer Cells." Cancers 11, no. 8 (August 2, 2019): 1105. http://dx.doi.org/10.3390/cancers11081105.

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Chromatin accessibility plays a critical factor in regulating gene expression in cancer cells. Several factors, including the High Mobility Group A (HMGA) family members, are known to participate directly in chromatin relaxation and transcriptional activation. The HMGA1 oncogene encodes an architectural chromatin transcription factor that alters DNA structure and interacts with transcription factors favouring their landing onto transcription regulatory sequences. Here, we provide evidence of an additional mechanism exploited by HMGA1 to modulate transcription. We demonstrate that, in a triple-negative breast cancer cellular model, HMGA1 sustains the action of epigenetic modifiers and in particular it positively influences both histone H3S10 phosphorylation by ribosomal protein S6 kinase alpha-3 (RSK2) and histone H2BK5 acetylation by CREB-binding protein (CBP). HMGA1, RSK2, and CBP control the expression of a set of genes involved in tumor progression and epithelial to mesenchymal transition. These results suggest that HMGA1 has an effect on the epigenetic status of cancer cells and that it could be exploited as a responsiveness predictor for epigenetic therapies in triple-negative breast cancers.

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Bhandari, Yuba R., Vinod Krishna, Rachael Powers, Sehej Parmar, Sara-Jayne Thursby, Ekta Gupta, Ozlem Kulak, et al. "Abstract A012: Transcription factor expression repertoire basis for epigenetic and transcriptional subtypes of colorectal cancers." Cancer Research 82, no. 23_Supplement_2 (December 1, 2022): A012. http://dx.doi.org/10.1158/1538-7445.cancepi22-a012.

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Abstract Colorectal cancers (CRCs) form a heterogenous group classified into epigenetic and transcriptional subtypes. The basis for the epigenetic subtypes, exemplified by varying degrees of promoter DNA hypermethylation, and its relation to the transcriptional subtypes is not well understood. We now link cancer-specific transcription factor (TF) expression dysregulation to methylation alterations near TF-binding sites at promoter and enhancer regions in CRCs and their pre-malignant precursor lesions to provide mechanistic insights into the origins and evolution of the CRC molecular subtypes. A gradient of TF-expression changes forms a basis for the subtypes of abnormal DNA methylation, termed CpG-island promoter DNA methylation phenotypes (CIMP), in CRCs and other cancers. CIMP is tightly correlated with cancer-specific hypermethylation at enhancers, which we term CpG-enhancer methylation phenotype (CEMP). CIMP/CEMP coordination appears to be driven by augmented downregulation of TFs with common binding sites at the hypermethylated enhancers and promoters. The dysregulated expression of TFs related to CIMP/CEMP subtypes occurs early during CRC development, detectable in pre-malignant adenomas. TF-based profiling further identifies patients with worse overall survival. Importantly, altered expression of these TFs discriminates the transcriptome-based consensus molecular subtypes (CMS), thus providing a common basis for CIMP and CMS subtypes. Citation Format: Yuba R. Bhandari, Vinod Krishna, Rachael Powers, Sehej Parmar, Sara-Jayne Thursby, Ekta Gupta, Ozlem Kulak, Prashanth Gokare, Joke Reumers, Liesbeth Van Wesenbeeck, Kurtis E. Bachman, Stephen B. Baylin, Hariharan Easwaran. Transcription factor expression repertoire basis for epigenetic and transcriptional subtypes of colorectal cancers. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Epigenomics; 2022 Oct 6-8; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_2):Abstract nr A012.

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Perera, Rushika M., Chiara Di Malta, and Andrea Ballabio. "MiT/TFE Family of Transcription Factors, Lysosomes, and Cancer." Annual Review of Cancer Biology 3, no. 1 (March 4, 2019): 203–22. http://dx.doi.org/10.1146/annurev-cancerbio-030518-055835.

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Cancer cells have an increased demand for energy sources to support accelerated rates of growth. When nutrients become limiting, cancer cells may switch to nonconventional energy sources that are mobilized through nutrient scavenging pathways involving autophagy and the lysosome. Thus, several cancers are highly reliant on constitutive activation of these pathways to degrade and recycle cellular materials. Here, we focus on the MiT/TFE family of transcription factors, which control transcriptional programs for autophagy and lysosome biogenesis and have emerged as regulators of energy metabolism in cancer. These new findings complement earlier reports that chromosomal translocations and amplifications involving the MiT/TFE genes contribute to the etiology and pathophysiology of renal cell carcinoma, melanoma, and sarcoma, suggesting pleiotropic roles for these factors in a wider array of cancers. Understanding the interplay between the oncogenic and stress-adaptive roles of MiT/TFE factors could shed light on fundamental mechanisms of cellular homeostasis and point to new strategies for cancer treatment.

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Harold, Cecelia M., Amber F. Buhagiar, Yan Cheng, and Susan J. Baserga. "Ribosomal RNA Transcription Regulation in Breast Cancer." Genes 12, no. 4 (March 29, 2021): 502. http://dx.doi.org/10.3390/genes12040502.

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Ribosome biogenesis is a complex process that is responsible for the formation of ribosomes and ultimately global protein synthesis. The first step in this process is the synthesis of the ribosomal RNA in the nucleolus, transcribed by RNA Polymerase I. Historically, abnormal nucleolar structure is indicative of poor cancer prognoses. In recent years, it has been shown that ribosome biogenesis, and rDNA transcription in particular, is dysregulated in cancer cells. Coupled with advancements in screening technology that allowed for the discovery of novel drugs targeting RNA Polymerase I, this transcriptional machinery is an increasingly viable target for cancer therapies. In this review, we discuss ribosome biogenesis in breast cancer and the different cellular pathways involved. Moreover, we discuss current therapeutics that have been found to affect rDNA transcription and more novel drugs that target rDNA transcription machinery as a promising avenue for breast cancer treatment.

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Zhang, Na, Tinghui Jiang, Yitao Wang, Lanyue Hu, and Youquan Bu. "BTG4 is A Novel p53 Target Gene That Inhibits Cell Growth and Induces Apoptosis." Genes 11, no. 2 (February 19, 2020): 217. http://dx.doi.org/10.3390/genes11020217.

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BTG4 is the last cloned and poorly studied member of BTG/Tob family. Studies have suggested that BTG4 is critical for the degradation of maternal mRNAs in mice during the process of maternal-to-zygotic transition, and downregulated in cancers, such as gastric cancer. However, the regulatory mechanism of BTG4 and its function in cancers remain elusive. In this study, we have for the first time identified the promoter region of the human BTG4 gene. Serial luciferase reporter assay demonstrated that the core promoter of BTG4 is mainly located within the 388 bp region near its transcription initiation site. Transcription factor binding site analysis revealed that the BTG4 promoter contains binding sites for canonical transcription factors, such as Sp1, whereas its first intron contains two overlapped consensus p53 binding sites. However, overexpression of Sp1 has negligible effects on BTG4 promoter activity, and site-directed mutagenesis assay further suggested that Sp1 is not a critical transcription factor for the transcriptional regulation of BTG4. Of note, luciferase assay revealed that one of the intronic p53 binding sites is highly responsive to p53. Both exogenous p53 overexpression and adriamycin-mediated endogenous p53 activation result in the transcriptional upregulation of BTG4. In addition, BTG4 is downregulated in lung and colorectal cancers, and overexpression of BTG4 inhibits cell growth and induces apoptosis in cancer cells. Taken together, our results strongly suggest that BTG4 is a novel p53-regulated gene and probably functions as a tumor suppressor in lung and colorectal cancers.

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Zhang, Fan, Maitree Biswas, Joseph Lee, Shreyas Lingadahalli, Samantha Wong, Christopher Wells, Neetu Saxena, et al. "Abstract 5729: Dynamic phase separation of the androgen receptor and its coactivators to regulate gene expression." Cancer Research 82, no. 12_Supplement (June 15, 2022): 5729. http://dx.doi.org/10.1158/1538-7445.am2022-5729.

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Abstract Numerous cancers, including prostate cancer (PCa), have been shown to be addicted to transcription programs driven by specific genomic sites known as superenhancers (SEs). Recently, it has been proposed that the robust transcription of genes at such SEs is enabled by the formation of phase-separated condensates by transcription factors and coactivators with intrinsically disordered regions. The androgen receptor (AR), the main oncogenic driver in PCa, contains large disordered regions and is co-recruited with the transcriptional coactivator MED1 to SEs in androgen-dependent prostate cancer cells, thereby promoting oncogenic transcriptional programs. In this work, we show that AR-rich, liquid-like foci form in prostate cancer models upon androgen stimulation. We reveal that foci formation correlates with AR transcriptional activity, which can be modulated by changing cellular foci content genetically or chemically. We also demonstrate that the transcriptional coactivator MED1 plays an essential role in the formation of transcriptionally active AR-rich foci and that AR antagonists that block cofactor recruitment or DNA binding hinder foci formation and thus AR transcriptional activity. The liquid like properties of the condensates were also validated in-vitro by using recombinant AR protein. Using clinical specimens, we detected the interaction between AR and MED1 in advanced forms of prostate cancer and not in benign tissues. These results suggest that enhanced compartmentalization of AR and coactivators at SEs may play an important role in the activation of oncogenic transcription programs in androgen-dependent PCa. A better understanding of the assembly and the regulation of these AR-rich compartments may provide novel therapeutic options for PCa by targeting downstream events of androgen activation and DNA binding of AR. Citation Format: Fan Zhang, Maitree Biswas, Joseph Lee, Shreyas Lingadahalli, Samantha Wong, Christopher Wells, Neetu Saxena, Bei Sun, Ana K. Parra-Nuñez, Christophe Sanchez, Jane Foo, Novia Chan, Lauren Ung, Nabeel Khan, Umut Berkay Altıntaş, Jennifer M. Bui, Yuzhuo Wang, Ladan Fazli, Paul S. Rennie, Nathan Lack, Artem Cherkasov, Martin E. Gleave, Joerg Gsponer, Nada Lallous. Dynamic phase separation of the androgen receptor and its coactivators to regulate gene expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5729.

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Maldonado, Edio, Sebastian Morales-Pison, Fabiola Urbina, Lilian Jara, and Aldo Solari. "Role of the Mediator Complex and MicroRNAs in Breast Cancer Etiology." Genes 13, no. 2 (January 26, 2022): 234. http://dx.doi.org/10.3390/genes13020234.

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Transcriptional coactivators play a key role in RNA polymerase II transcription and gene regulation. One of the most important transcriptional coactivators is the Mediator (MED) complex, which is an evolutionary conserved large multiprotein complex. MED transduces the signal between DNA-bound transcriptional activators (gene-specific transcription factors) to the RNA polymerase II transcription machinery to activate transcription. It is known that MED plays an essential role in ER-mediated gene expression mainly through the MED1 subunit, since estrogen receptor (ER) can interact with MED1 by specific protein–protein interactions; therefore, MED1 plays a fundamental role in ER-positive breast cancer (BC) etiology. Additionally, other MED subunits also play a role in BC etiology. On the other hand, microRNAs (miRNAs) are a family of small non-coding RNAs, which can regulate gene expression at the post-transcriptional level by binding in a sequence-specific fashion at the 3′ UTR of the messenger RNA. The miRNAs are also important factors that influence oncogenic signaling in BC by acting as both tumor suppressors and oncogenes. Moreover, miRNAs are involved in endocrine therapy resistance of BC, specifically to tamoxifen, a drug that is used to target ER signaling. In metazoans, very little is known about the transcriptional regulation of miRNA by the MED complex and less about the transcriptional regulation of miRNAs involved in BC initiation and progression. Recently, it has been shown that MED1 is able to regulate the transcription of the ER-dependent miR-191/425 cluster promoting BC cell proliferation and migration. In this review, we will discuss the role of MED1 transcriptional coactivator in the etiology of BC and in endocrine therapy-resistance of BC and also the contribution of other MED subunits to BC development, progression and metastasis. Lastly, we identified miRNAs that potentially can regulate the expression of MED subunits.

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Huh, Hyunbin, Dong Kim, Han-Sol Jeong, and Hyun Park. "Regulation of TEAD Transcription Factors in Cancer Biology." Cells 8, no. 6 (June 17, 2019): 600. http://dx.doi.org/10.3390/cells8060600.

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Transcriptional enhanced associate domain (TEAD) transcription factors play important roles during development, cell proliferation, regeneration, and tissue homeostasis. TEAD integrates with and coordinates various signal transduction pathways including Hippo, Wnt, transforming growth factor beta (TGFβ), and epidermal growth factor receptor (EGFR) pathways. TEAD deregulation affects well-established cancer genes such as KRAS, BRAF, LKB1, NF2, and MYC, and its transcriptional output plays an important role in tumor progression, metastasis, cancer metabolism, immunity, and drug resistance. To date, TEADs have been recognized to be key transcription factors of the Hippo pathway. Therefore, most studies are focused on the Hippo kinases and YAP/TAZ, whereas the Hippo-dependent and Hippo-independent regulators and regulations governing TEAD only emerged recently. Deregulation of the TEAD transcriptional output plays important roles in tumor progression and serves as a prognostic biomarker due to high correlation with clinicopathological parameters in human malignancies. In addition, discovering the molecular mechanisms of TEAD, such as post-translational modifications and nucleocytoplasmic shuttling, represents an important means of modulating TEAD transcriptional activity. Collectively, this review highlights the role of TEAD in multistep-tumorigenesis by interacting with upstream oncogenic signaling pathways and controlling downstream target genes, which provides unprecedented insight and rationale into developing TEAD-targeted anticancer therapeutics.

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Mirabelli, Caitlynn N., Rachel La Selva, John Heath, Steven Hébert, Jutta Steinberger, Jialin Jiang, Claudia Kleinman, Sidong Huang, and Josie Ursini-Siegel. "Abstract 126: Defining how oxidative stress drives the evolution of aggressive breast cancers." Cancer Research 82, no. 12_Supplement (June 15, 2022): 126. http://dx.doi.org/10.1158/1538-7445.am2022-126.

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Abstract Breast cancer is the most commonly diagnosed malignancy in women worldwide. It is a molecularly heterogeneous disease, which poses difficulties in the treatment of more advanced cancers. Despite this fact, the mechanisms contributing to the emergence of aggressive breast cancers remains poorly understood. We focus on reactive oxygen species (ROS), which are induced by a variety of stimuli in breast cancer cells. Moderately elevated ROS levels are tumor-promoting and facilitate the emergence of more aggressive tumours. Our laboratory has developed a unique model of HER2+ breast cancer that evolved to acquire more aggressive properties under conditions of chronic oxidative stress. We identified 20 transcription factors/co-regulators that were specifically overexpressed in these aggressive breast cancers, compared to their parental counterparts. We hypothesize that these transcription factors are central to the ability of breast tumors to adapt to chronic oxidative stress and acquire more aggressive properties. To test this, I have performed an in vivo functional shRNA screen to identify those transcriptional regulators that drive an aggressive phenotype. This will be followed by functional validation studies to interrogate whether and how these unique transcription factors overexpressed in aggressive breast cancers impact tumour growth, metastasis, and drug resistance. Mechanistically, we will explore whether and how these transcriptional responses mediate adaptive responses to tumor microenvironmental stressors, including altered metabolism, hypoxia, and tumor immune responses. This research will broaden our understanding of how breast cancers adapt to oxidative stress responses and represents a necessary first step in the development of novel therapeutics against these invulnerable malignancies. Citation Format: Caitlynn N. Mirabelli, Rachel La Selva, John Heath, Steven Hébert, Jutta Steinberger, Jialin Jiang, Claudia Kleinman, Sidong Huang, Josie Ursini-Siegel. Defining how oxidative stress drives the evolution of aggressive breast cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 126.

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Bloor, Adrian, Ekaterina Kotsopoulou, Penny Hayward, Brian Champion, and Anthony Green. "RFP represses transcriptional activation by bHLH transcription factors." Oncogene 24, no. 45 (June 27, 2005): 6729–36. http://dx.doi.org/10.1038/sj.onc.1208828.

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Yuan, Fuwen, William Hankey, Dayong Wu, Hongyan Wang, Jason Somarelli, Andrew J. Armstrong, Jiaoti Huang, Zhong Chen, and Qianben Wang. "Molecular determinants for enzalutamide-induced transcription in prostate cancer." Nucleic Acids Research 47, no. 19 (September 10, 2019): 10104–14. http://dx.doi.org/10.1093/nar/gkz790.

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Abstract Enzalutamide, a second-generation androgen receptor (AR) antagonist, has demonstrated clinical benefit in men with prostate cancer. However, it only provides a temporary response and modest increase in survival, indicating a rapid evolution of resistance. Previous studies suggest that enzalutamide may function as a partial transcriptional agonist, but the underlying mechanisms for enzalutamide-induced transcription remain poorly understood. Here, we show that enzalutamide stimulates expression of a novel subset of genes distinct from androgen-responsive genes. Treatment of prostate cancer cells with enzalutamide enhances recruitment of pioneer factor GATA2, AR, Mediator subunits MED1 and MED14, and RNA Pol II to regulatory elements of enzalutamide-responsive genes. Mechanistically, GATA2 globally directs enzalutamide-induced transcription by facilitating AR, Mediator and Pol II loading to enzalutamide-responsive gene loci. Importantly, the GATA2 inhibitor K7174 inhibits enzalutamide-induced transcription by decreasing binding of the GATA2/AR/Mediator/Pol II transcriptional complex, contributing to sensitization of prostate cancer cells to enzalutamide treatment. Our findings provide mechanistic insight into the future combination of GATA2 inhibitors and enzalutamide for improved AR-targeted therapy.

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Wu, Guojun, Motonobu Osada, Zhongmin Guo, Alexey Fomenkov, Shahnaz Begum, Ming Zhao, Sunil Upadhyay, et al. "ΔNp63α Up-Regulates the Hsp70 Gene in Human Cancer." Cancer Research 65, no. 3 (February 1, 2005): 758–66. http://dx.doi.org/10.1158/0008-5472.758.65.3.

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Abstract HSP70, a stress response protein, is known to be a determinant of cell death and cell transformation. We show that different isoforms of p63 have different transcriptional activities on hsp70 genes. ΔNp63α, an abundantly expressed isoform of p63, activates (in vitro and in vivo), whereas TAp63γ down-regulates the expression of hsp70. We further show that the transactivation domain at the NH2 terminus of p63 represses, whereas the COOH terminus activates hsp70 transcription. In addition, ΔNp63α regulates transcription of the hsp70 gene through its interaction with the CCAAT binding factor and NF-Y transcription factors which are known to form a complex with the CCAAT box located in the hsp70 promoter. Moreover, ΔNp63α expression correlates with HSP70 expression in all head and neck cancer cell lines. Finally, we show colocalization of ΔNp63α and HSP70 in the epithelium and coexpression of both proteins in 41 primary head and neck cancers. Our study provides strong evidence for the physiologic association between ΔNp63α and hsp70 in human cancer, thus further supporting the oncogenic potential of ΔNp63α.

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Chen, Xiaoxin, Yahui Li, Chorlada Paiboonrungruang, Yong Li, Heiko Peters, Ralf Kist, and Zhaohui Xiong. "PAX9 in Cancer Development." International Journal of Molecular Sciences 23, no. 10 (May 17, 2022): 5589. http://dx.doi.org/10.3390/ijms23105589.

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Paired box 9 (PAX9) is a transcription factor of the PAX family functioning as both a transcriptional activator and repressor. Its functional roles in the embryonic development of various tissues and organs have been well studied. However, its roles and molecular mechanisms in cancer development are largely unknown. Here, we review the current understanding of PAX9 expression, upstream regulation of PAX9, and PAX9 downstream events in cancer development. Promoter hypermethylation, promoter SNP, microRNA, and inhibition of upstream pathways (e.g., NOTCH) result in PAX9 silencing or downregulation, whereas gene amplification and an epigenetic axis upregulate PAX9 expression. PAX9 may contribute to carcinogenesis through dysregulation of its transcriptional targets and related molecular pathways. In summary, extensive studies on PAX9 in its cellular and tissue contexts are warranted in various cancers, in particular, HNSCC, ESCC, lung cancer, and cervical SCC.

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Koutsi, Marianna A., Marialena Pouliou, Lydia Champezou, Giannis Vatsellas, Angeliki-Ioanna Giannopoulou, Christina Piperi, and Marios Agelopoulos. "Typical Enhancers, Super-Enhancers, and Cancers." Cancers 14, no. 18 (September 8, 2022): 4375. http://dx.doi.org/10.3390/cancers14184375.

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Non-coding segments of the human genome are enriched in cis-regulatory modules that constitute functional elements, such as transcriptional enhancers and Super-enhancers. A hallmark of cancer pathogenesis is the dramatic dysregulation of the “archetype” gene expression profiles of normal human cells. Genomic variations can promote such deficiencies when occurring across enhancers and Super-enhancers, since they affect their mechanistic principles, their functional capacity and specificity, and the epigenomic features of the chromatin microenvironment across which these regulatory elements reside. Here, we comprehensively describe: fundamental mechanisms of gene expression dysregulation in cancers that involve genomic abnormalities within enhancers’ and Super-enhancers’ (SEs) sequences, which alter the expression of oncogenic transcription factors (TFs); cutting-edge technologies applied for the analysis of variation-enriched hotspots of the cancer genome; and pharmacological approaches for the treatment of Super-enhancers’ aberrant function. Finally, we provide an intratumor meta-analysis, which highlights that genomic variations in transcription-factor-driven tumors are accompanied overexpression of genes, a portion of which encodes for additional cancer-related transcription factors.

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Liu, Li-Yu D., Li-Yun Chang, Wen-Hung Kuo, Hsiao-Lin Hwa, Ming-Kwang Shyu, King-Jen Chang, and Fon-Jou Hsieh. "In Silico Prediction for Regulation of Transcription Factors on Their Shared Target Genes Indicates Relevant Clinical Implications in a Breast Cancer Population." Cancer Informatics 11 (January 2012): CIN.S8470. http://dx.doi.org/10.4137/cin.s8470.

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Aberrant transcriptional activities have been documented in breast cancers. Studies often find some transcription factors to be inappropriately regulated and enriched in certain pathological states. The promoter regions of most target genes have binding sites for their transcription factors. An ample of evidence supports their combinatorial effect on their shared target gene expressions. Here, we used a new statistic method, bivariate CID, to predict combinatorial interaction activity between ERα and a transcription factor (E2F1or GATA3 or ERRα) in regulating target gene expression via four regulatory mechanisms. We identified gene sets in three signal transduction pathways perturbed in breast tumors: cell cycle, VEGF, and PDGFRB. Bivariate network analysis revealed several target genes previously implicated in tumor angiogenesis are among the predicted shared targets, including VEGFA, PDGFRB. In summary, our analysis suggests the importance for the multivariate space of an inferred ERα transcriptional regulatory network in breast cancer diagnostic and therapeutic development.

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Taniuchi, Fumiko, Koji Higai, Tomomi Tanaka, Yutaro Azuma, and Kojiro Matsumoto. "Transcriptional Regulation ofFucosyltransferase 1Gene Expression in Colon Cancer Cells." Scientific World Journal 2013 (2013): 1–9. http://dx.doi.org/10.1155/2013/105464.

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Theα1,2-fucosyltransferase I (FUT1) enzyme is important for the biosynthesis of H antigens, Lewis B, and Lewis Y. In this study, we clarified the transcriptional regulation of FUT1 in the DLD-1 colon cancer cell line, which has high expression of Lewis B and Lewis Y antigens, expresses theFUT1gene, and showsα1,2-fucosyltransferase (FUT) activity. 5′-rapid amplification of cDNA ends revealed a FUT1 transcriptional start site −10 nucleotides upstream of the site registered at NM_000148 in the DataBase of Human Transcription Start Sites (DBTSS). Using the dual luciferase assay,FUT1gene expression was shown to be regulated at the region −91 to −81 nt to the transcriptional start site, which contains the Elk-1 binding site. Site-directed mutagenesis of this region revealed the Elk-1 binding site to be essential for FUT1 transcription. Furthermore, transfection of the dominant negative Elk-1 gene, and the chromatin immunoprecipitation (CHIp) assay, supported Elk-1-dependent transcriptional regulation ofFUT1gene expression in DLD-1 cells. These results suggest that a defined region in the 5′-flanking region of FUT1 is critical for FUT1 transcription and that constitutive gene expression ofFUT1is regulated by Elk-1 in DLD-1 cells.

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Laqtom, Nouf N., Khloud M. Algothmi, and Amani H. Bakhribah. "Inferring Transcription Factors and microRNAs Associated with Elevated Expression of the Oncogenic B-Cell Lymphoma 11A in Triple Negative Breast Cancer." Journal of King Abdulaziz University - Medical Sciences 23, no. 3 (September 30, 2016): 9–21. http://dx.doi.org/10.4197/med.23-3.2.

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B-cell lymphoma 11A, a transcriptional repressor, is highly expressed in triple negative breast cancer. The in vitro studies and animal models provide initial evidence suggesting that the knockdown of B-cell lymphoma 11A has a therapeutic eff ect on breast cancer. Defining the regulators driving the high expression of B-cell lymphoma 11A is important to understand its cancer-related functions. Among these regulators, transcription factors and microRNAs are critical for gene expression and associated with expression perturbations. Firstly, weidentifi ed the transcription factors that potentially interact with B-cell lymphoma 11A promoter. Based on bioinformatics prediction and multiple Omics datasets, two upregulated transcriptional activators Zinc Finger BED-Type Containing 4 and E2F Transcription Factor 1 in triple negative breast cancer were found to have seven sites within B-cell lymphoma 11A promoter. Secondly, we aimed to determine a putative set of microRNA that can mediate the post-transcriptional repression of B-cell lymphoma 11A. miR-513a-5p, miR-139-5p, miR-1179, miR-140-5p, and miR-542-3p, harboring at least one site of interaction with B-cell lymphoma 11A 3 untranslated region, were found inhibited in triple negative breast cancer. Taken together, the combinatorial regulation by transcription factors and microRNAs provide valuable information for further investigation on controlling the expression level of B-cell lymphoma 11A in triple negative breast cancer.

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Benz, C. C. "Transcription factors and breast cancer." Endocrine Related Cancer 5, no. 4 (December 1, 1998): 271–82. http://dx.doi.org/10.1677/erc.0.0050271.

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Vervoort, Stephin J., Jennifer R. Devlin, Nicholas Kwiatkowski, Mingxing Teng, Nathanael S. Gray, and Ricky W. Johnstone. "Targeting transcription cycles in cancer." Nature Reviews Cancer 22, no. 1 (October 21, 2021): 5–24. http://dx.doi.org/10.1038/s41568-021-00411-8.

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Piulats, Jaume, and Gema Tarrasón. "E2F transcription factors and cancer." Revista de Oncología 3, no. 5 (September 2001): 241–49. http://dx.doi.org/10.1007/bf02719883.

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Zheng, R., and G. A. Blobel. "GATA Transcription Factors and Cancer." Genes & Cancer 1, no. 12 (December 1, 2010): 1178–88. http://dx.doi.org/10.1177/1947601911404223.

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Schmid, Roland M., Susanne Liptay, Hans Weidenbach, and Guido Adler. "Transcription Factors in Pancreatic Cancer." Digestive Surgery 11, no. 3-6 (1994): 160–63. http://dx.doi.org/10.1159/000172248.

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Bhagwat, Anand S., and Christopher R. Vakoc. "Targeting Transcription Factors in Cancer." Trends in Cancer 1, no. 1 (September 2015): 53–65. http://dx.doi.org/10.1016/j.trecan.2015.07.001.

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Cantelli, Gaia, Eva Crosas-Molist, Mirella Georgouli, and Victoria Sanz-Moreno. "TGFΒ-induced transcription in cancer." Seminars in Cancer Biology 42 (February 2017): 60–69. http://dx.doi.org/10.1016/j.semcancer.2016.08.009.

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Trzyna, Elzbieta. "Regulation of transcription in cancer." Frontiers in Bioscience 17, no. 1 (2012): 316. http://dx.doi.org/10.2741/3929.

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Thorne, James L., Moray J. Campbell, and Bryan M. Turner. "Transcription factors, chromatin and cancer." International Journal of Biochemistry & Cell Biology 41, no. 1 (January 2009): 164–75. http://dx.doi.org/10.1016/j.biocel.2008.08.029.

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Maity, Subhajit, Artem Gridnev, and Jyoti R. Misra. "Assays Used for Discovering Small Molecule Inhibitors of YAP Activity in Cancers." Cancers 14, no. 4 (February 17, 2022): 1029. http://dx.doi.org/10.3390/cancers14041029.

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YAP/TAZ are transcriptional coactivators that function as the key downstream effectors of Hippo signaling. They are commonly misregulated in most human cancers, which exhibit a higher level of expression and nuclear localization of YAP/TAZ, and display addiction to YAP-dependent transcription. In the nucleus, these coactivators associate with TEA domain transcription factors (TEAD1-4) to regulate the expression of genes that promote cell proliferation and inhibit cell death. Together, this results in an excessive growth of the cancerous tissue. Further, YAP/TAZ play a critical role in tumor metastasis and chemotherapy resistance by promoting cancer stem cell fate. Furthermore, they affect tumor immunity by promoting the expression of PD-L1. Thus, YAP plays an important role in multiple aspects of cancer biology and thus, provides a critical target for cancer therapy. Here we discuss various assays that are used for conducting high-throughput screens of small molecule libraries for hit identification, and subsequent hit validation for successful discovery of potent inhibitors of YAP-transcriptional activity. Furthermore, we describe the advantages and limitations of these assays.

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Shats, Igor, Michael L. Gatza, Beiyu Liu, Steven P. Angus, Lingchong You, and Joseph R. Nevins. "FOXO Transcription Factors Control E2F1 Transcriptional Specificity and Apoptotic Function." Cancer Research 73, no. 19 (August 21, 2013): 6056–67. http://dx.doi.org/10.1158/0008-5472.can-13-0453.

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Chai, Jian Yi, Vaisnevee Sugumar, Mohammed Abdullah Alshawsh, Won Fen Wong, Aditya Arya, Pei Pei Chong, and Chung Yeng Looi. "The Role of Smoothened-Dependent and -Independent Hedgehog Signaling Pathway in Tumorigenesis." Biomedicines 9, no. 9 (September 10, 2021): 1188. http://dx.doi.org/10.3390/biomedicines9091188.

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The Hedgehog (Hh)-glioma-associated oncogene homolog (GLI) signaling pathway is highly conserved among mammals, with crucial roles in regulating embryonic development as well as in cancer initiation and progression. The GLI transcription factors (GLI1, GLI2, and GLI3) are effectors of the Hh pathway and are regulated via Smoothened (SMO)-dependent and SMO-independent mechanisms. The SMO-dependent route involves the common Hh-PTCH-SMO axis, and mutations or transcriptional and epigenetic dysregulation at these levels lead to the constitutive activation of GLI transcription factors. Conversely, the SMO-independent route involves the SMO bypass regulation of GLI transcription factors by external signaling pathways and their interacting proteins or by epigenetic and transcriptional regulation of GLI transcription factors expression. Both routes of GLI activation, when dysregulated, have been heavily implicated in tumorigenesis of many known cancers, making them important targets for cancer treatment. Hence, this review describes the various SMO-dependent and SMO-independent routes of GLI regulation in the tumorigenesis of multiple cancers in order to provide a holistic view of the paradigms of hedgehog signaling networks involving GLI regulation. An in-depth understanding of the complex interplay between GLI and various signaling elements could help inspire new therapeutic breakthroughs for the treatment of Hh-GLI-dependent cancers in the future. Lastly, we have presented an up-to-date summary of the latest findings concerning the use of Hh inhibitors in clinical developmental studies and discussed the challenges, perspectives, and possible directions regarding the use of SMO/GLI inhibitors in clinical settings.

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Regner, Matthew J., Aatish Thennavan, Kamila Wisniewska, Susana Garcia-Recio, Raul Mendez-Giraldez, Philip Spanheimer, Charles M. Perou, and Hector L. Franco. "Abstract P5-14-02: Identifying oncogenic enhancer elements in TNBC of the Basal-like subtype using single-cell ATAC-seq and RNA-seq." Cancer Research 83, no. 5_Supplement (March 1, 2023): P5–14–02—P5–14–02. http://dx.doi.org/10.1158/1538-7445.sabcs22-p5-14-02.

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Abstract Identification of the cis-regulatory elements controlling oncogenic transcriptional programs is critical to understanding tumor biology. To find cis-regulatory elements (i.e. gene enhancers) of oncogenic dependencies in Triple-Negative Breast Cancers (TNBC) of the Basal-like gene expression subtype, we generated matched single-cell transcriptome (scRNA-seq) and chromatin accessibility (scATAC-seq) profiles for two human Basal-like tumors and four normal mammary reduction samples. This unique dataset enabled us to correlate variations in chromatin structure with variations in gene expression revealing putative enhancers that are specifically active within cancer cells, but not within normal mammary ductal epithelial cells. We then leveraged the Cancer Dependency Map (DepMap) portal at the BROAD Institute to infer gene expression dependencies in breast cancer cell lines of the Basal-like molecular subtype. Putative cancer-specific enhancers were prioritized based on the transcriptional dependency of their target gene(s) in Basal-like cell lines as reported by the DepMap portal. Based on our preliminary analyses, we report several cancer-specific enhancers that drive the expression of important transcription factors such as EN1 and SOX4. These transcription factors are known to have profound effects on tumor biology, especially considering that high expression of EN1 is associated with brain metastasis and SOX4 is known to regulate immune evasion and PI3K/Akt signaling. Moreover, both of these transcription factors portend a worse outcome in TNBC patients. Thus, our analysis suggests that high levels of expression of these transcription factors is sustained specifically within the malignant cell types of these tumors, by the activity of these cancer-specific enhancers that are not typically active in normal epithelial cells. We are now performing CRISPR dCas9-KRAB experiments to epigenetically silence these cancer-specific enhancers and measure the consequences on expression of their predicted target genes. Additionally, we are investigating the trans-acting transcription factors that may physically bind to these enhancers to further regulate oncogenic transcription. By defining the regulatory logic of cancer cells at single-cell resolution, our work highlights the importance of cancer-specific and clinically relevant oncogenic regulatory elements in TNBC of the Basal-like subtype. Citation Format: Matthew J. Regner, Aatish Thennavan, Kamila Wisniewska, Susana Garcia-Recio, Raul Mendez-Giraldez, Philip Spanheimer, Charles M. Perou, Hector L. Franco. Identifying oncogenic enhancer elements in TNBC of the Basal-like subtype using single-cell ATAC-seq and RNA-seq [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-14-02.

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Jones, Cheyenne A., William P. Tansey, and April M. Weissmiller. "Emerging Themes in Mechanisms of Tumorigenesis by SWI/SNF Subunit Mutation." Epigenetics Insights 15 (January 2022): 251686572211156. http://dx.doi.org/10.1177/25168657221115656.

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The SWI/SNF chromatin remodeling complex uses the energy of ATP hydrolysis to alter contacts between DNA and nucleosomes, allowing regions of the genome to become accessible for biological processes such as transcription. The SWI/SNF chromatin remodeler is also one of the most frequently altered protein complexes in cancer, with upwards of 20% of all cancers carrying mutations in a SWI/SNF subunit. Intense studies over the last decade have probed the molecular events associated with SWI/SNF dysfunction in cancer and common themes are beginning to emerge in how tumor-associated SWI/SNF mutations promote malignancy. In this review, we summarize current understanding of SWI/SNF complexes, their alterations in cancer, and what is known about the impact of these mutations on tumor-relevant transcriptional events. We discuss how enhancer dysregulation is a common theme in SWI/SNF mutant cancers and describe how resultant alterations in enhancer and super-enhancer activity conspire to block development and differentiation while promoting stemness and self-renewal. We also identify a second emerging theme in which SWI/SNF perturbations intersect with potent oncoprotein transcription factors AP-1 and MYC to drive malignant transcriptional programs.

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Anose, Bynthia M., and Michel M. Sanders. "Androgen Receptor Regulates Transcription of the ZEB1 Transcription Factor." International Journal of Endocrinology 2011 (2011): 1–10. http://dx.doi.org/10.1155/2011/903918.

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The zinc finger E-box binding protein 1 (ZEB1) transcription factor belongs to a two-member family of zinc-finger homeodomain proteins involved in physiological and pathological events mostly relating to cell migration and epithelial to mesenchymal transitions (EMTs). ZEB1 (also known as δEF1, zfhx1a, TCF8, and Zfhep) plays a key role in regulating such diverse processes as T-cell development, skeletal patterning, reproduction, and cancer cell metastasis. However, the factors that regulate its expression and consequently the signaling pathways in which ZEB1 participates are poorly defined. Because it is induced by estrogen and progesterone and is high in prostate cancer, we investigated whethertcf8, which encodes ZEB1, is regulated by androgen. Data herein demonstrate thattcf8is induced by dihydrotestosterone (DHT) in the human PC-3/AR prostate cancer cell line and that this induction is mediated by two androgen response elements (AREs). These results demonstrate that ZEB1 is an intermediary in androgen signaling pathways.

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Journal articles on the topic 'Cancer transcription'

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