Non-redundant Functions of EMT Transcription Factors

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2019 Jan 4

PMID 30602760

Citations 264

Authors

Marc P Stemmler

Rebecca L Eccles

Simone Brabletz

Thomas Brabletz

Affiliations

Soon will be listed here.

Abstract

Epithelial-mesenchymal transition (EMT) is a crucial embryonic programme that is executed by various EMT transcription factors (EMT-TFs) and is aberrantly activated in cancer and other diseases. However, the causal role of EMT and EMT-TFs in different disease processes, especially cancer and metastasis, continues to be debated. In this Review, we identify and describe specific, non-redundant functions of the different EMT-TFs and discuss the reasons that may underlie disputes about EMT in cancer.

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References

Nieto M, Huang R, Jackson R, Thiery J . EMT: 2016. Cell. 2016; 166(1):21-45. DOI: 10.1016/j.cell.2016.06.028. View

Puisieux A, Brabletz T, Caramel J . Oncogenic roles of EMT-inducing transcription factors. Nat Cell Biol. 2014; 16(6):488-94. DOI: 10.1038/ncb2976. View

Huang R, Zong X . Aberrant cancer metabolism in epithelial-mesenchymal transition and cancer metastasis: Mechanisms in cancer progression. Crit Rev Oncol Hematol. 2017; 115:13-22. DOI: 10.1016/j.critrevonc.2017.04.005. View

Sciacovelli M, Frezza C . Metabolic reprogramming and epithelial-to-mesenchymal transition in cancer. FEBS J. 2017; 284(19):3132-3144. PMC: 6049610. DOI: 10.1111/febs.14090. View

Brabletz T . To differentiate or not--routes towards metastasis. Nat Rev Cancer. 2012; 12(6):425-36. DOI: 10.1038/nrc3265. View

Nieto M, Cano A . The epithelial-mesenchymal transition under control: global programs to regulate epithelial plasticity. Semin Cancer Biol. 2012; 22(5-6):361-8. DOI: 10.1016/j.semcancer.2012.05.003. View

Pastushenko I, Brisebarre A, Sifrim A, Fioramonti M, Revenco T, Boumahdi S . Identification of the tumour transition states occurring during EMT. Nature. 2018; 556(7702):463-468. DOI: 10.1038/s41586-018-0040-3. View

Varga J, Greten F . Cell plasticity in epithelial homeostasis and tumorigenesis. Nat Cell Biol. 2017; 19(10):1133-1141. DOI: 10.1038/ncb3611. View

Ledford H . Cancer theory faces doubts. Nature. 2011; 472(7343):273. DOI: 10.1038/472273a. View

10.

Tarin D, Thompson E, Newgreen D . The fallacy of epithelial mesenchymal transition in neoplasia. Cancer Res. 2005; 65(14):5996-6000. DOI: 10.1158/0008-5472.CAN-05-0699. View

11.

Friedl P, Gilmour D . Collective cell migration in morphogenesis, regeneration and cancer. Nat Rev Mol Cell Biol. 2009; 10(7):445-57. DOI: 10.1038/nrm2720. View

12.

Bronsert P, Enderle-Ammour K, Bader M, Timme S, Kuehs M, Csanadi A . Cancer cell invasion and EMT marker expression: a three-dimensional study of the human cancer-host interface. J Pathol. 2014; 234(3):410-22. DOI: 10.1002/path.4416. View

13.

Aiello N, Brabletz T, Kang Y, Nieto M, Weinberg R, Stanger B . Upholding a role for EMT in pancreatic cancer metastasis. Nature. 2017; 547(7661):E7-E8. PMC: 5830071. DOI: 10.1038/nature22963. View

14.

Brabletz T, Kalluri R, Nieto M, Weinberg R . EMT in cancer. Nat Rev Cancer. 2018; 18(2):128-134. DOI: 10.1038/nrc.2017.118. View

15.

Maheswaran S, Haber D . Cell fate: Transition loses its invasive edge. Nature. 2015; 527(7579):452-3. DOI: 10.1038/nature16313. View

16.

Santamaria P, Moreno-Bueno G, Portillo F, Cano A . EMT: Present and future in clinical oncology. Mol Oncol. 2017; 11(7):718-738. PMC: 5496494. DOI: 10.1002/1878-0261.12091. View

17.

Ye X, Brabletz T, Kang Y, Longmore G, Nieto M, Stanger B . Upholding a role for EMT in breast cancer metastasis. Nature. 2017; 547(7661):E1-E3. PMC: 6283276. DOI: 10.1038/nature22816. View

18.

Fischer K, Durrans A, Lee S, Sheng J, Li F, Wong S . Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance. Nature. 2015; 527(7579):472-6. PMC: 4662610. DOI: 10.1038/nature15748. View

19.

Zheng X, Carstens J, Kim J, Scheible M, Kaye J, Sugimoto H . Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer. Nature. 2015; 527(7579):525-530. PMC: 4849281. DOI: 10.1038/nature16064. View

20.

Krebs A, Mitschke J, Losada M, Schmalhofer O, Boerries M, Busch H . The EMT-activator Zeb1 is a key factor for cell plasticity and promotes metastasis in pancreatic cancer. Nat Cell Biol. 2017; 19(5):518-529. DOI: 10.1038/ncb3513. View