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Epithelial-to-mesenchymal transition in cancer: complexity and opportunities
Yun Zhang, Robert A. Weinberg
Frontiers of Medicine · 2018 · Review
Abstract
The cell-biological program termed the epithelial-to-mesenchymal transition (EMT) plays an important role in both development and cancer progression. Depending on the contextual signals and intracellular gene circuits of a particular cell, this program can drive fully epithelial cells to enter into a series of phenotypic states arrayed along the epithelial-mesenchymal phenotypic axis. These cell states display distinctive cellular characteristics, including stemness, invasiveness, drug-resistance and the ability to form metastases at distant organs, and thereby contribute to cancer metastasis and relapse. Currently we still lack a coherent overview of the molecular and biochemical mechanisms inducing cells to enter various states along the epithelial-mesenchymal phenotypic spectrum. An improved understanding of the dynamic and plastic nature of the EMT program has the potential to yield novel therapies targeting this cellular program that may aid in the management of high-grade malignancies.
References 112
- 1.
Nieto MA, Huang RYJ, Jackson RA, Thiery JP. EMT: 2016. Cell 2016; 166(1): 21–45
Not in our library10.1016/j.cell.2016.06.028
- 2.
Polyak K, Weinberg RA. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer 2009; 9(4): 265–273
Not in our library10.1038/nrc2620
- 3.
Greenburg G, Hay ED. Epithelia suspended in collagen gels can lose polarity and express characteristics of migrating mesenchymal cells. J Cell Biol 1982; 95(1): 333–339
Not in our library10.1083/jcb.95.1.333
- 4.
Lim J, Thiery JP. Epithelial-mesenchymal transitions: insights from development. Development 2012; 139(19): 3471–3486
Not in our library10.1242/dev.071209
- 5.
Carver EA, Jiang R, Lan Y, Oram KF, Gridley T. The mouse snail gene encodes a key regulator of the epithelial-mesenchymal transition. Mol Cell Biol 2001; 21(23): 8184–8188
Not in our library10.1128/mcb.21.23.8184-8188.2001
- 6.
Chen ZF, Behringer RR. twist is required in head mesenchyme for cranial neural tube morphogenesis. Genes Dev 1995; 9(6): 686–699
Not in our library10.1101/gad.9.6.686
- 7.
Van de Putte T, Maruhashi M, Francis A, Nelles L, Kondoh H, Huylebroeck D, Higashi Y. Mice lacking ZFHX1B, the gene that codes for Smad-interacting protein-1, reveal a role for multiple neural crest cell defects in the etiology of Hirschsprung disease-mental retardation syndrome. Am J Hum Genet 2003; 72(2): 465–470
Not in our library10.1086/346092
- 8.
Jiang R, Lan Y, Norton CR, Sundberg JP, Gridley T. The Slug gene is not essential for mesoderm or neural crest development in mice. Dev Biol 1998; 198(2): 277–285
Not in our library
- 9.
Higashi Y, Moribe H, Takagi T, Sekido R, Kawakami K, Kikutani H, Kondoh H. Impairment of T cell development in δEF1 mutant mice. J Exp Med 1997; 185(8): 1467–1479
Not in our library10.1084/jem.185.8.1467
- 10.
Shibue T, Weinberg RA. EMT, CSCs, and drug resistance: the mechanistic link and clinical implications. Nat Rev Clin Oncol 2017; 14(10): 611–629
Not in our library10.1038/nrclinonc.2017.44
- 11.
Shaw TJ, Martin P. Wound repair: a showcase for cell plasticity and migration. Curr Opin Cell Biol 2016; 42: 29–37
Not in our library10.1016/j.ceb.2016.04.001
- 12.
Ye X, Weinberg RA. Epithelial-mesenchymal plasticity: a central regulator of cancer progression. Trends Cell Biol 2015; 25(11): 675–686
Not in our library10.1016/j.tcb.2015.07.012
- 13.
Lambert AW, Pattabiraman DR, Weinberg RA. Emerging biological principles of metastasis. Cell 2017; 168(4): 670–691
Not in our library10.1016/j.cell.2016.11.037
- 14.
Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2002; 2(6): 442–454
Not in our library10.1038/nrc822
- 15.
Thompson L, Chang B, Barsky SH. Monoclonal origins of malignant mixed tumors (carcinosarcomas). Evidence for a divergent histogenesis. Am J Surg Pathol 1996; 20(3): 277–285
Not in our library10.1097/00000478-199603000-00003
- 16.
Tsai JH, Yang J. Epithelial-mesenchymal plasticity in carcinoma metastasis. Genes Dev 2013; 27(20): 2192–2206
Not in our library10.1101/gad.225334.113
- 17.
Ocaña OH, Córcoles R, Fabra A, Moreno-Bueno G, Acloque H, Vega S, Barrallo-Gimeno A, Cano A, Nieto MA. Metastatic colonization requires the repression of the epithelial-mesenchymal transition inducer Prrx1. Cancer Cell 2012; 22(6): 709–724
Not in our library10.1016/j.ccr.2012.10.012
- 18.
Tsai JH, Donaher JL, Murphy DA, Chau S, Yang J. Spatiotemporal regulation of epithelial-mesenchymal transition is essential for squamous cell carcinoma metastasis. Cancer Cell 2012; 22(6): 725–736
Not in our library10.1016/j.ccr.2012.09.022
- 19.
Lawson DA, Bhakta NR, Kessenbrock K, Prummel KD, Yu Y, Takai K, Zhou A, Eyob H, Balakrishnan S, Wang CY, Yaswen P, Goga A, Werb Z. Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells. Nature 2015; 526(7571): 131–135
Not in our library10.1038/nature15260
- 20.
Pattabiraman DR, Weinberg RA. Tackling the cancer stem cells—what challenges do they pose? Nat Rev Drug Discov 2014; 13(7): 497–512
Not in our library10.1038/nrd4253
- 21.
Brabletz T, Jung A, Spaderna S, Hlubek F, Kirchner T. Opinion: migrating cancer stem cells — an integrated concept of malignant tumour progression. Nat Rev Cancer 2005; 5(9): 744–749
Not in our library10.1038/nrc1694
- 22.
Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA. The epithelialmesenchymal transition generates cells with properties of stem cells. Cell 2008; 133(4): 704–715
Not in our library10.1016/j.cell.2008.03.027
- 23.
Guo W, Keckesova Z, Donaher JL, Shibue T, Tischler V, Reinhardt F, Itzkovitz S, Noske A, Zürrer-Härdi U, Bell G, Tam WL, Mani SA, van Oudenaarden A, Weinberg RA. Slug and Sox9 cooperatively determine the mammary stem cell state. Cell 2012; 148(5): 1015–1028
Not in our library10.1016/j.cell.2012.02.008
- 24.
- 25.
Rasheed ZA, Yang J, Wang Q, Kowalski J, Freed I, Murter C, Hong SM, Koorstra JB, Rajeshkumar NV, He X, Goggins M, Iacobuzio-Donahue C, Berman DM, Laheru D, Jimeno A, Hidalgo M, Maitra A, Matsui W. Prognostic significance of tumorigenic cells with mesenchymal features in pancreatic adenocarcinoma. J Natl Cancer Inst 2010; 102(5): 340–351
Not in our library10.1093/jnci/djp535
- 26.
- 27.
- 28.
Long H, Xiang T, Qi W, Huang J, Chen J, He L, Liang Z, Guo B, Li Y, Xie R, Zhu B. CD133+ ovarian cancer stem-like cells promote non-stem cancer cell metastasis via CCL5 induced epithelial-mesenchymal transition. Oncotarget 2015; 6(8): 5846–5859
Not in our library10.18632/oncotarget.3462
- 29.
Ye X, Tam WL, Shibue T, Kaygusuz Y, Reinhardt F, Ng Eaton E, Weinberg RA. Distinct EMT programs control normal mammary stem cells and tumour-initiating cells. Nature 2015; 525(7568): 256–260
Not in our library10.1038/nature14897
- 30.
Chaffer CL, Brueckmann I, Scheel C, Kaestli AJ, Wiggins PA, Rodrigues LO, Brooks M, Reinhardt F, Su Y, Polyak K, Arendt LM, Kuperwasser C, Bierie B, Weinberg RA. Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state. Proc Natl Acad Sci U S A 2011; 108(19): 7950–7955
Not in our library10.1073/pnas.1102454108
- 31.
Chaffer CL, Marjanovic ND, Lee T, Bell G, Kleer CG, Reinhardt F, D’Alessio AC, Young RA, Weinberg RA. Poised chromatin at the ZEB1 promoter enables breast cancer cell plasticity and enhances tumorigenicity. Cell 2013; 154(1): 61–74
Not in our library10.1016/j.cell.2013.06.005
- 32.
Del Pozo Martin Y, Park D, Ramachandran A, Ombrato L, Calvo F, Chakravarty P, Spencer-Dene B, Derzsi S, Hill CS, Sahai E, Malanchi I. Mesenchymal cancer cell-stroma crosstalk promotes niche activation, epithelial reversion, and metastatic colonization. Cell Rep 2015; 13(11): 2456–2469
Not in our library10.1016/j.celrep.2015.11.025
- 33.
Bierie B, Pierce SE, Kroeger C, Stover DG, Pattabiraman DR, Thiru P, Liu Donaher J, Reinhardt F, Chaffer CL, Keckesova Z, Weinberg RA. Integrin-β4 identifies cancer stem cell-enriched populations of partially mesenchymal carcinoma cells. Proc Natl Acad Sci U S A 2017; 114(12): E2337–E2346
Not in our library10.1073/pnas.1618298114
- 34.
Mehlen P, Puisieux A. Metastasis: a question of life or death. Nat Rev Cancer 2006; 6(6): 449–458
Not in our library10.1038/nrc1886
- 35.
Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, Savagner P, Gitelman I, Richardson A, Weinberg RA. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 2004; 117(7): 927–939
Not in our library10.1016/j.cell.2004.06.006
- 36.
Krebs AM, Mitschke J, Lasierra Losada M, Schmalhofer O, Boerries M, Busch H, Boettcher M, Mougiakakos D, Reichardt W, Bronsert P, Brunton VG, Pilarsky C, Winkler TH, Brabletz S, Stemmler MP, Brabletz T. 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
Not in our library10.1038/ncb3513
- 37.
Friedl P, Locker J, Sahai E, Segall JE. Classifying collective cancer cell invasion. Nat Cell Biol 2012; 14(8): 777–783
Not in our library10.1038/ncb2548
- 38.
Friedl P, Gilmour D. Collective cell migration in morphogenesis, regeneration and cancer. Nat Rev Mol Cell Biol 2009; 10(7): 445–457
Not in our library10.1038/nrm2720
- 39.
Cheung KJ, Padmanaban V, Silvestri V, Schipper K, Cohen JD, Fairchild AN, Gorin MA, Verdone JE, Pienta KJ, Bader JS, Ewald AJ. Polyclonal breast cancer metastases arise from collective dissemination of keratin 14-expressing tumor cell clusters. Proc Natl Acad Sci U S A 2016; 113(7): E854–E863
Not in our library10.1073/pnas.1508541113
- 40.
Aceto N, Bardia A, Miyamoto DT, Donaldson MC, Wittner BS, Spencer JA, Yu M, Pely A, Engstrom A, Zhu H, Brannigan BW, Kapur R, Stott SL, Shioda T, Ramaswamy S, Ting DT, Lin CP, Toner M, Haber DA, Maheswaran S. Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell 2014; 158(5): 1110–1122
Not in our library10.1016/j.cell.2014.07.013
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