Epithelial-mesenchymal Transition and Its Transcription Factors

Overview

Journal Biosci Rep

Specialty Cell Biology

Date 2021 Oct 28

PMID 34708244

Citations 85

Authors

Pallabi Debnath

Rohit Singh Huirem

Paloma Dutta

Santanu Palchaudhuri

Affiliations

Soon will be listed here.

Abstract

Epithelial-mesenchymal transition or EMT is an extremely dynamic process involved in conversion of epithelial cells into mesenchymal cells, stimulated by an ensemble of signaling pathways, leading to change in cellular morphology, suppression of epithelial characters and acquisition of properties such as enhanced cell motility and invasiveness, reduced cell death by apoptosis, resistance to chemotherapeutic drugs etc. Significantly, EMT has been found to play a crucial role during embryonic development, tissue fibrosis and would healing, as well as during cancer metastasis. Over the years, work from various laboratories have identified a rather large number of transcription factors (TFs) including the master regulators of EMT, with the ability to regulate the EMT process directly. In this review, we put together these EMT TFs and discussed their role in the process. We have also tried to focus on their mechanism of action, their interdependency, and the large regulatory network they form. Subsequently, it has become clear that the composition and structure of the transcriptional regulatory network behind EMT probably varies based upon various physiological and pathological contexts, or even in a cell/tissue type-dependent manner.

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References

Oliemuller E, Newman R, Tsang S, Foo S, Muirhead G, Noor F . SOX11 promotes epithelial/mesenchymal hybrid state and alters tropism of invasive breast cancer cells. Elife. 2020; 9. PMC: 7518891. DOI: 10.7554/eLife.58374. View

Liu B, Liu J, Yu H, Wang C, Kong C . Transcription factor RUNX2 regulates epithelial‑mesenchymal transition and progression in renal cell carcinomas. Oncol Rep. 2020; 43(2):609-616. DOI: 10.3892/or.2019.7428. View

Stanisavljevic J, Porta-de-la-Riva M, Batlle R, Garcia de Herreros A, Baulida J . The p65 subunit of NF-κB and PARP1 assist Snail1 in activating fibronectin transcription. J Cell Sci. 2012; 124(Pt 24):4161-71. DOI: 10.1242/jcs.078824. View

Simpson P . Maternal-Zygotic Gene Interactions during Formation of the Dorsoventral Pattern in Drosophila Embryos. Genetics. 1983; 105(3):615-32. PMC: 1202177. DOI: 10.1093/genetics/105.3.615. View

Kong F, Sun T, Kong X, Xie D, Li Z, Xie K . Krüppel-like Factor 4 Suppresses Serine/Threonine Kinase 33 Activation and Metastasis of Gastric Cancer through Reversing Epithelial-Mesenchymal Transition. Clin Cancer Res. 2018; 24(10):2440-2451. PMC: 6765216. DOI: 10.1158/1078-0432.CCR-17-3346. View

Shi Y, Sawada J, Sui G, Affar E, Whetstine J, Lan F . Coordinated histone modifications mediated by a CtBP co-repressor complex. Nature. 2003; 422(6933):735-8. DOI: 10.1038/nature01550. View

Kong F, Qu Z, Yuan H, Wang J, Zhao M, Guo Y . Overexpression of FOXM1 is associated with EMT and is a predictor of poor prognosis in non-small cell lung cancer. Oncol Rep. 2014; 31(6):2660-8. DOI: 10.3892/or.2014.3129. View

Masui T, Ota I, Yook J, Mikami S, Yane K, Yamanaka T . Snail-induced epithelial-mesenchymal transition promotes cancer stem cell-like phenotype in head and neck cancer cells. Int J Oncol. 2013; 44(3):693-9. DOI: 10.3892/ijo.2013.2225. View

Eger A, Aigner K, Sonderegger S, Dampier B, Oehler S, Schreiber M . DeltaEF1 is a transcriptional repressor of E-cadherin and regulates epithelial plasticity in breast cancer cells. Oncogene. 2005; 24(14):2375-85. DOI: 10.1038/sj.onc.1208429. View

10.

Gammill L, Bronner-Fraser M . Neural crest specification: migrating into genomics. Nat Rev Neurosci. 2003; 4(10):795-805. DOI: 10.1038/nrn1219. View

11.

Wang H, Wang Z, Li Y, Lu T, Hu G . Silencing Snail Reverses Epithelial-Mesenchymal Transition and Increases Radiosensitivity in Hypopharyngeal Carcinoma. Onco Targets Ther. 2020; 13:497-511. PMC: 6970617. DOI: 10.2147/OTT.S237410. View

12.

Ning X, Zhang K, Wu Q, Liu M, Sun S . Emerging role of Twist1 in fibrotic diseases. J Cell Mol Med. 2018; 22(3):1383-1391. PMC: 5824384. DOI: 10.1111/jcmm.13465. View

13.

Sun S, Liu D, Deng Y, Zhang X, Wan D, Xi B . SIX1 coordinates with TGFβ signals to induce epithelial-mesenchymal transition in cervical cancer. Oncol Lett. 2016; 12(2):1271-1278. PMC: 4950046. DOI: 10.3892/ol.2016.4797. View

14.

Blanco M, Moreno-Bueno G, Sarrio D, Locascio A, Cano A, Palacios J . Correlation of Snail expression with histological grade and lymph node status in breast carcinomas. Oncogene. 2002; 21(20):3241-6. DOI: 10.1038/sj.onc.1205416. View

15.

Ocana O, Corcoles R, Fabra A, Moreno-Bueno G, Acloque H, Vega S . Metastatic colonization requires the repression of the epithelial-mesenchymal transition inducer Prrx1. Cancer Cell. 2012; 22(6):709-24. DOI: 10.1016/j.ccr.2012.10.012. View

16.

Jiang R, Lan Y, Norton C, Sundberg J, Gridley T . The Slug gene is not essential for mesoderm or neural crest development in mice. Dev Biol. 1998; 198(2):277-85. View

17.

Prislei S, Martinelli E, Zannoni G, Petrillo M, Filippetti F, Mariani M . Role and prognostic significance of the epithelial-mesenchymal transition factor ZEB2 in ovarian cancer. Oncotarget. 2015; 6(22):18966-79. PMC: 4662468. DOI: 10.18632/oncotarget.3943. View

18.

Mani S, Yang J, Brooks M, Schwaninger G, Zhou A, Miura N . Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers. Proc Natl Acad Sci U S A. 2007; 104(24):10069-74. PMC: 1891217. DOI: 10.1073/pnas.0703900104. View

19.

Batlle E, Sancho E, Franci C, Dominguez D, Monfar M, Baulida J . The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol. 2000; 2(2):84-9. DOI: 10.1038/35000034. View

20.

Li M, Wang J, Yang S, Li W, Xiao L, He Y . ZEB2 promotes tumor metastasis and correlates with poor prognosis of human colorectal cancer. Am J Transl Res. 2017; 9(6):2838-2851. PMC: 5489885. View