Epithelial-mesenchymal Transition in Tumor Tissue and Its Role for Metastatic Spread of Cancer
Authors:
V. M. Matějka 1,2; J. Fínek 1; M. Králíčková 2
Authors place of work:
Onkologická a radioterapeutická klinika LF UK a FN Plzeň
1; Ústav histologie a embryologie, LF UK v Plzni
2
Published in the journal:
Klin Onkol 2017; 30(1): 20-27
Category:
Review
doi:
https://doi.org/10.14735/amko201720
Summary
Background:
Metastasis, recurrence, and resistance to chemotherapy are leading causes of the majority of cancer-related mortality worldwide. The process of metastasis can be artificially divided into a series of sequential, highly organized, and organ-specific steps. The underlying mechanisms are still poorly understood, but are believed to be mediated by epithelial-mesenchymal transition (EMT). First described in embryogenesis, EMT is a cellular reprogramming process in which epithelial cells acquire a mesenchymal phenotype. During this transformation, epithelial cells lose their shape, epithelial markers, and ability to grow in colonies. They acquire a spindle-shaped morphology and exhibit more motile and invasive behavior. These phenotypic changes are associated with modifications in different interconnected protein and gene families, such as transcription factors, cadherins, catenins, matrix metalloproteases, and growth receptors. EMT has been observed in many cancers, such as breast, ovarian, colon, and esophageal cancers, and is associated with poor prognosis and metastasis. Also, resistance to cytotoxic treatments is associated with reactivation of embryonic programs. Understanding this process is necessary to provide a better understanding of cancer progression and could lead to the development of new therapeutic or prognostic strategies for the treatment of cancer.
Conclusion:
This article summarizes the known molecular pathways involved in EMT in cancer.
Key words:
epithelial-mesenchymal transition – carcinoma – metastasis
The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.
The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.
Submitted:
24. 6. 2016
Accepted:
14. 11. 2016
Zdroje
1. Dusek L, Muzik J, Maluskova D et al. Epidemiology of cancers with implemented screening programmes in an international comparison. Klin Onkol 2014; 27 (Suppl 2): 2S40–2S48. doi: 10.14735/amko20142S40.
2. Yeatman TJ, Nicolson GL. Molecular basis of tumor progression: mechanisms of organ-specific tumor metastasis. Sem Sur Onco 1993; 9 (3): 256–263.
3. Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest 2009; 119 (6): 1420–1428. doi: 10.1172/JCI39104.
4. Chui MH. Insights into cancer metastasis from a clinicopathologicperspective: epithelial-mesenchymal transition is not a necessary step. Int J Cancer 2013; 132 (7): 1487–1495. doi: 10.1002/ijc.27745.
5. Wan L, Pantel K, Kang Y. Tumormetastasis: moving new biological insights into the clinic. Nat Med 2013; 19 (11): 1450–1464. doi: 10.1038/nm.3391.
6. Thiery JP, Sleeman JP. Complex networks orchestrace epithelial-mesenchymal transitions. Nat Rev Mol Cell Biology 2006; 7 (2): 131–142.
7. Hay ED. An overview of epithelio-mesenchymal transformation. Acta Anat (Basel) 1995; 154 (1): 8–20.
8. Hay ED. The mesenchymal cell, its role in the embryo, and the remarkable signaling mechanisms that create it. Dev Dyn 2005; 233 (3): 706–720.
9. Heisenberg CP, Solnica-Krezel L. Back and forth between cell fate specification and movement during vertebrate gastrulation. Curr Opin Genet Dev 2008; 18 (4): 311–316. doi: 10.1016/j.gde.2008.07.011.
10. Solnica-Krezel L. Conserved patterns of cell movements during vertebrate gastrulation. Curr Biol 2005; 15 (6): 213–228.
11. Tucker RP. Neural crest cells: a model for invasive behavior. Int J Biochem Cell Biol 2004; 36 (2): 173–177.
12. Duband JL, Thiery JP. Appearance and distribution of fibronectin during chick embryo gastrulation and neurulation. Dev Biol 1982; 94 (2): 337–350.
13. Mercado-Pimentel ME, Runyan RB. Multiple transforming growth factor-beta isoforms and receptors function during epithelial-mesenchymal cell transformation in the embryonic heart. Cells Tissues Organs 2007; 185 (1–3): 146–156.
14. Inai K, Norris RA, Hoffman S et al. BMP-2 induces cell migration and periostin expression during atrioventricular valvulogenesis. Dev Biol 2008; 315 (2): 383–396. doi: 10.1016/j.ydbio.2007.12.028.
15. Liebner S, Cattelino A, Gallini R et al. Beta-catenin is required for endothelial-mesenchymal transformation during heart cushion development in the mouse. J Cell Biol 2004; 166 (3): 359–367.
16. Chen YH, Ishii M, Sucov HM et al. Msx1 and Msx2 are required for endothelial-mesenchymal transformation of the atrioventricular cushions and patterning of the atrioventricular myocardium. BMC Dev Biol 2008; 8: 75. doi: 10.1186/1471-213X-8-75.
17. Romano LA, Runyan RB. Slug is an essential target of TGFbeta2 signaling in the developing chicken heart. Dev Biol 2000; 223 (1): 91–102.
18. Thiery JP, Acloque H, Huang RY et al. Epithelial-mesenchymal transitions in development and disease. Cell 2009; 139 (5): 871–890. doi: 10.1016/j.cell.2009.11.007.
19. Strutz F, Okada H, Lo CW et al. Identification and characterization of a fibroblast marker: FSP1. J Cell Biol 1995; 130 (2): 393–405.
20. Okada H, Danoff TM, Kalluri R et al. Early role of Fsp1 in epithelial-mesenchymal transformation. Am J Physiol 1997; 273 (4 Pt 2): F563–F574.
21. Zeisberg EM, Tarnavski O, Zeisberg M et al. Endothelial-tomesenchymal transition contributes to cardiac fibrosis. Nat Med 2007; 13 (8): 952–961.
22. Kim KK, Kugler MC, Wolters PJ et al. Alveolar epithelial cell mesenchymal transition develops in vivo during pulmonary fibrosis and is regulated by the extracellular matrix. Proc Natl Acad Sci U S A 2006; 103 (35): 13180–13185.
23. Rastaldi MP, Ferrario F, Giardino L et al. Epithelial-mesenchymal transition of tubular epithelial cells in human renal biopsies. Kidney Int 2002; 62 (1): 137–146.
24. Zeisberg M, Yang C, Martino M et al. Fibroblasts derive from hepatocytes in liver fibrosis via epithelial to mesenchymal transition. J Biol Chem 2007; 282 (32): 23337–23347.
25. Zeisberg M, Hanai J, Sugimoto H et al. BMP-7 counteracts TGFbeta1-induced epithelial-to-mesenchymal transitiv and reverses chronic renal injury. Nat Med 2003; 9 (7): 964–968.
26. Rastaldi MP, Ferrario F, Giardino L et al. Epithelial-mesenchymal transition of tubular epithelial cells in human renal biopsies. Kidney Int 2002; 62 (1): 137–146.
27. Bataille F, Rohrmeier C, Bates R et al. Evidence for a role of epithelial mesenchymal transition during pathogenesis of fistulae in Crohn’s disease. Inflamm Bowel Dis 2008; 14 (11): 1514–1527. doi: 10.1002/ibd.20590.
28. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100 (1): 57–70.
29. Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2002; 2 (6): 442–454.
30. Yang J, Weinberg RA. Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell 2008; 14 (6): 818–829. doi: 10.1016/j.devcel.2008.05.009.
31. Fidler IJ, Poste G. The „seed and soil“ hypothesis revisited. Lancet Oncol 2008; 9 (8): 808. doi: 10.1016/S1470-2045 (08) 70201-8.
32. Brabletz T, Jung A, Reu S et al. Variable beta-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment. Proc Natl Acad Sci U S A 2001; 98 (18): 10356–10361.
33. Zeisberg M, Shah AA, Kalluri R. Bone morphogenic protein-7 induces mesenchymal to epithelial transition in adult renal fibroblasts and facilitates regeneration of injured kidney. J Biol Chem 2005; 280 (9): 8094–8100.
34. Jechlinger M, Grunert S, Beug H. Mechanisms in epithelial plasticity and metastasis: insights from 3D cultures and expression profiling. J Mammary Gland Biol Neoplasia 2002; 7 (4): 415–432.
35. Bissell MJ, Radisky DC, Rizki A et al. The organizing principle: microenvironmental influences in the normal and malignant breast. Differentiation 2002; 70 (9–10): 537–546.
36. Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2002; 2 (6): 442–454.
37. Shi Y, Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 2003; 113 (6): 685–700.
38. Niessen K, Fu Y, Chang L et al. Slug is a direct Notch target required for initiation of cardiac cushion cellularization. J Cell Biol 2008; 182 (2): 315–325. doi: 10.1083/jcb.200710067.
39. Medici D, Hay ED, Olsen BR. Snail and Slug promote epithelial-mesenchymal transitiv through beta-catenin-T-cell factor-4-dependent expression of transforming growth factorbeta3. Mol Biol Cell 2008; 19: 4875–4887.
40. Kokudo T, Suzuki Y, Yoshimatsu Y et al. Snail is required for TGF{beta}-induced endothelial-mesenchymal transitiv of embryonic stem cell-derived endothelial cells. J Cell Sci 2008; 121 (Pt 20): 3317–3324. doi: 10.1242/jcs.028282.
41. Tse JC, Kalluri R. Mechanisms of metastasis: epithelial-to-mesenchymal transitiv and contribution of tumor microenvironment. J Cell Biochem 2007; 101 (4): 816–829.
42. Gupta PB, Mani S, Yang J et al. The evolving portrait of cancer metastasis. Cold Spring Harb Symp Quant Biol 2005; 70: 291–297.
43. Yang J, Mani SA, Weinberg RA. Exploring a new twist on tumor metastasis. Cancer Res 2006; 66 (9): 4549–4552.
44. Mani SA, Yang J, Brooks M et al. 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): 10069–10074.
45. Mani SA, Guo W, Liao MJ et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008; 133 (4): 704–715. doi: 10.1016/j.cell.2008.03.027.
46. Hartwell KA, Muir B, Reinhardt F et al. The Spemann organizer gene, Goosecoid, promotes tumor metastasis. Proc Natl Acad Sci U S A 2006; 103 (50): 18969–18974.
47. Bierie B, Moses HL. Tumour microenvironment: TGFbeta: the molecular Jekyll and Hyde of cancer. Nat Rev Cancer 2006; 6 (7): 506–520.
48. Oft M, Heider KH, Beug H. TGFbeta signaling is necessary for carcinoma cell invasiveness and metastasis. Curr Biol 1998; 8 (23): 1243–1252.
49. Hata A, Shi Y, Massague J. TGF-beta signaling and cancer: structural and functional consequences of mutations in Smads. Mol Med Today 1998; 4 (6): 257–262.
50. Song J. EMT or apoptosis: a decision for TGF-beta. Cell Res 2007; 17 (4): 289–290.
51. Miyazono K, ten Dijke P, Heldin CH. TGF-beta signaling by Smad proteins. Adv Immunol 2000; 75: 115–157.
52. Derynck R, Akhurst RJ, Balmain A. TGF-beta signaling in tumor suppression and cancer progression. Nat Genet 2001; 29 (2): 117–129.
53. Heldin CH, Miyazono K, ten Dijke P. TGF-beta signalling from cell membrane to nukleus through SMAD proteins. Nature 1997; 390 (6659): 465–471.
54. Roberts AB, Tian F, Byfield SD et al. Smad3 is key to TGFbeta-mediated epithelial-to-mesenchymal transition, fibrosis, tumor suppression and metastasis. Cytokine Growth Factor Rev 2006; 17 (1–2): 19–27.
55. Piek E, Moustakas A, Kurisaki A et al. TGF- (beta) type I receptor/ALK-5 and Smad proteins mediate epithelial to mesenchymal transdifferentiation in NMuMG breast epithelial cells. J Cell Sci 1999; 112 (Pt 24): 4557–4568.
56. Bhowmick NA, Ghiassi M, Bakin A et al. Transforming growth factor-beta1 mediates epithelial to mesenchymal transdifferentiation through a RhoA-dependent mechanism. Mol Biol Cell 2001; 12 (1): 27–36.
57. Saika S, Ikeda K, Yamanaka O et al. Transient adenoviral gene transfer of Smad7 prevents injury-induced epithelial-mesenchymal transition of lens epithelium in mice. Lab Invest 2004; 84 (10): 1259–1270.
58. Bhowmick NA, Zent R, Ghiassi M et al. Integrin beta 1 signaling is necessary for transforming growth factor-beta activation of p38MAPK and epithelial plasticity. J Biol Chem 2001; 276 (50): 46707–46713.
59. Lee YH, Albig AR, Maryann R et al. Fibulin-5 initiates epithelial-mesenchymal transition (EMT) and enhances EMT induced by TGF-beta in mammary epithelial cells via a MMP-dependent mechanism. Carcinogenesis 2008; 29 (12): 2243–2251. doi: 10.1093/carcin/bgn 199.
60. Janda E, Lehmann K, Killisch I et al. Ras and TGF[beta] cooperatively regulate epithelial cell plasticity and metastasis: dissection of Ras signaling pathways. J Cell Biol 2002; 156 (2): 299–313.
61. Cui W, Fowlis DJ, Bryson S et al. TGFbeta1 inhibits the formation of benign skin tumors, but enhances progression to invasive spindle carcinomas in transgenic mice. Cell 1996; 86 (4): 531–542.
62. Watanabe T, Wu TT, Catalano PJ et al. Molecular predictors of survival after adjuvant chemotherapy for colon cancer. N Engl J Med 2001; 344 (16): 1196–1206.
63. Katsuno Y, Lamouille S, Derynck R et al. TGF-beta signaling end epithelial-mezenchymal transition in cancer progression. Curr Opin Oncol 2013; 25 (1): 76–84. doi: 10.1097/CCO.0b013e32835b6371.
64. Tepass U, Truong K, Godt D et al. Cadherins in embryonic and neural morphogenesis. Nat Rev Mol Cell Biol 2000; 1 (2): 91–100.
65. Edelman GM, Gallin WJ, Delouvee A et al. Early epochal maps of two different cell adhesion molecules. Proc Natl Acad Sci U S A 1983; 80 (14): 4384–4388.
66. Gottardi CJ, Wong E, Gumbiner BM. E-cadherin suppresses cellular transformation by inhibiting beta-catenin signaling in an adhesionindependent manner. J Cell Biol 2001; 153 (5): 1049–1060.
67. Kim K, Lu Z, Hay ED. Direct evidence for a role of beta-catenin/LEF-1 signaling pathway in induction of EMT. Cell Biol Int 2002; 26 (5): 463–476.
68. Muta H, Noguchi M, Kanai Y et al. E-cadherin gene mutations in signet ring cell carcinoma of the stomach. Jpn J Cancer Res 1995; 87 (8): 843–848.
69. Saito A, Kanai Y, Maesawa C et al. Disruption of E-cadherinmediated cell adhesion systems in gastric cancers in young patients. Jpn J Cancer Res 1999; 90 (9): 993–999.
70. Hirohashi S. Inactivation of the E-cadherinmediated cell adhesion system in human cancers. Am J Pathol 1998; 153 (2): 333–339.
71. Birchmeier W, Behrens J. Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness. Biochim Biophys Acta 1994; 1198 (1): 11–26.
72. Blanco MJ, Moreno-Bueno G, Sarrio D et al. Correlation of Snail expression with histological grade and lymph node status in breast carcinomas. Oncogene 2002; 21 (20): 3241–3246.
73. Yokoyama K, Kamata N, Hayashi E et al. Reverse correlation of E-cadherin and snail expression in oral squamous cell carcinoma cells in vitro. Oral Oncol 2001; 37 (1): 65–71.
74. Miele L, Golde T, Osborne B et al. NOTCH signaling ain cancer. Curr Mol Med 2006; 6 (8): 905–918.
75. Miele L, Miao H, Nickoloff BJ et al. NOTCH signaling as a novel cancer therapeutic target. Curr Cancer Drug Targets 2006; 6 (4): 313–323.
76. Penton AL, Leonard LD, Spinner NB et al. Notch signaling in human development and disease. Semin Cell Dev Biol 2012; 23 (4): 450–457. doi: 10.1016/j.semcdb.2012.01.010.
77. Wang T, Xuan X, Pian L et al. Notch-1-mediated esophageal carcinoma EC-9706 cell invasion and metastasis by inducing epithelial-mesenchymal transition through Snail. Tumour Biol 2014; 35 (2): 1193–1201.
78. Ishida T, Hijioka H, Kume K et al. Notch signaling induces EMT in OSCC cell lines in a hypoxic enviroment. Oncol Lett 2013; 6 (5): 1201–1206.
79. Nusse R, Fuerer C, Ching W et al. Wnt signaling and stem cell control. Cold Spring Harb Symp Quant Biol 2008; 73: 59–66. doi: 10.1101/sqb.2008.73.035.
80. Clevers H, Nusse R. Wnt/beta-catenin signaling and disease. Cell 2012; 149 (6): 1192–1205. doi: 10.1016/j.cell.2012.05.012.
81. Guo J, Fu Z, Wei J et al. PRRX1 promotes epithelial-mezenchymal transition through the Wnt/beta-catenin pathways in gastric cancer. Med Oncol 2015; 32 (1): 393. doi: 10.1007/s12032-014-0393-x.
82. Beachy PA, Karhadkar SS, Berman DM et al. Tissue repair and stem cell renewal in carcinogenesis. Nature 2004; 432 (7015): 324–331.
83. Lei J, Ma J, Ma Q et al. Hedgehog signaling regulates hypoxia induced epithelial to mesenchymal transition and invasion in pancreatic cancer cells via a ligand-independent manne. Mol Cancer 2013; 12: 66. doi: 10.1186/1476-4598-12-66.
84. Cano A, Nieto MA. Non-coding RNAs take centre stage in epithelial-to-mesenchymal transition. Trends Cell Biol 2008; 18 (8): 357–359. doi: 10.1016/j.tcb.2008.05.005.
85. Christoffersen NR, Silahtaroglu A, Orom UA et al. MiR-200b mediates post-transcriptional repression of ZFHX1B. RNA 2007; 13 (8): 1172–1178.
86. Park SM, Gaur AB, Lengyel E et al. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev 2008; 22 (7): 894–907. doi: 10.1101/gad.1640 608.
87. Gregory PA, Bert AG, Paterson EL et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol 2008; 10 (5): 593–601. doi: 10.1038/ncb1722.
88. Burk U, Schubert J, Wellner U et al. A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Rep 2008; 9 (6): 582–589. doi: 10.1038/embor.2008.74.
89. Bracken CP, Gregory PA, Kolesnikoff N et al. A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition. Cancer Res 2008; 68 (19): 7846–7854. doi: 10.1158/0008-5472.CAN-08-1942.
90. Camps C, Buffa FM, Colella S et al. hsa-miR-210 Is induced by hypoxia and is an independent prognostic factor in breast cancer. Clin Cancer Res 2008; 14 (5): 1340–1348. doi: 10.1158/1078-0432.CCR-07-1755.
91. Fu X, Han Y, Wu Y et al. Prognostic role of microRNA-21 in various carcinomas: a systematic review and meta-analysis. Eur J Clin Invest 2011; 41 (11): 1245–1253. doi: 10.1111/j.1365-2362.2011.02535.x.
92. Mei M, Ren Y, Zhou X et al. Downregulation of miR-21 enhances chemotherapeutic effect of taxol in breast carcinoma cells. Technol Cancer Res Treat 2010; 9 (1): 77–86.
93. Iorio MV, Casalini P, Piovan C et al. MicroRNA-205 regulates HER3 in human breast cancer. Cancer Res 2009; 69 (6): 2195–2200. doi: 10.1158/0008-5472.CAN-08-2920.
94. Kumarswamy R, Mudduluru G, Ceppi P et al. MicroRNA-30a inhibits epithelial-to-mesenchymal transition by targeting Snai1 and is downregulated in non-small cell lung cancer. Int J Cancer 2012; 130 (9): 2044–2053. doi: 10.1002/ijc.26218.
95. Yang AD, Fan F, Camp ER. Chronic oxaliplatin resistence induces epithelial-to-mesenchymal transition in colorectal cancer cell lines. Clin Cancer Res 2006; 12 (14 Pt 1): 4147–4753.
96. Papageorgis P, Cheng K, Ozturk S et al. Smad4 inactivation promotes malignancy and drug resistence of colon cance. Cancer Res 2011; 71 (3): 998–1008. doi: 10.1158/0008-5472.CAN-09-3269.
97. Hoshinono H, Miyoshi N, Nagai K et al. Epithelial-mesenchymal transition with expression of SNAIl-induced chemoresistance in colorectal cancer. Biochem Biophys Res Commun 2009; 390 (3): 1061–1065. doi: 10.1016/j.bbrc.2009.10.117.
98. Chen X, Wang Y, Xia H et al. Loss of E-cadherin promotes the growth, invasion and drug resistence of colorectal cancer cells and is associated with liver metastasis. Mol Biol Rep 2012; 39 (6): 6707–6714. doi: 10.1007/s11033-012-1494-2.
99. Buck E, Eyzaguirre A, Barr S et al. Loss of homotypic cell adhesion by epithelial-mesenchymal transition or mutation limits sensitivity to epidermal growth factor receptor inhibition. Mol Cancer Ther 2007; 6 (2): 532–541.
100. Trumpp A, Wiestler OD. Mechanisms of disease: cancer stem cells – targeting the evil twin. Nat Clin Pact Oncol 2008; 5 (6): 337–347. doi: 10.1038/ncponc1110.
101. Fan CW, Chen T, Shang YN et al. Cancer-initiating cells derived from human rectal adenocarcinoma tissues carry mesenchymal phenotypes and resist drug therapies. Cell Death Dis 2013; 4: e828. doi: 10.1038/cddis.2013.337.
102. Hirano T, Satow R, Kato A et al. Identification of novel small compounds that restore E-cadherin expression and inhibit tumor cell motility and invasiveness. Biochem Pharmacol 2013; 86 (10): 1419–1429. doi: 10.1016/j.bcp.2013.09.001.
103. Fernando RI, Litzinger M, Trono P et al. The T-box transcription factor Brachyury promotes epithelial-mesenchymal transition in human tumor cells. J Clin Invest 2010; 120 (2): 533–544. doi: 10.1172/JCI38379.
104. Roselli M, Fernando RI, Guadagni F et al. Brachyury, a driver of the epithelial-mesenchymal transition, is overexpressed in human lung tumors: an opportunity for novel interventions against lung cancer. Clin Cancer Res 2012; 18 (14): 3868–3879. doi: 10.1158/1078-0432.CCR-11-3211.
105. Chua KN, Sim WJ, Racine V et al. A cell-based small molecule screening method for identifying inhibitors of epithelial-mesenchymal ransition in carcinoma. PLoS One 2012; 7 (3): e33183. doi: 10.1371/journal.pone.0033183.
106. Flanigan SA, Pitts TM, Newton TP et al. Overcoming IGF1R/1R resistence through inhibiton of MEK signaling in colorectal cance models. Clin Cancer Res 2013; 19: 6219–6129. doi: 10.1158/1078-0432.CCR-13-0145.
107. Bocca C, Bozzo F, Cannito S et al. Celecoxib inactivates epithelial-mesenchymal transition stimulated by hypoxia and/or epidermal growth factor in colon cancer cells. Mol Carcinog 2012; 51 (10): 783–795.
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