Epithelial Mesenchymal Transformation
DOI:
https://doi.org/10.12974/2309-6160.2014.02.01.4Keywords:
Epithelial-mesenchymal transition, carsinogenesis, metastasesAbstract
The epithelial-mesenchymal transition (EMT) defined as a process by which epithelial cells lose their cell polarity and cell-cell adhesion, and gain migratory and invasive properties to transform into mesenchymal cells. Some signaling events activated transcription factors (Wnt, TGF-b, and FGF family members) that mediate EMT. EMTBeginning of metastasis needs invasion, which is allowed by EMT. Carcinoma cells in primary tumor lose intercellular adhesion mediated by E-cadherin repression and break through the basement membrane with increased invasive properties, and enter the bloodstream through intravasation. After then, when these circulating tumor cells (CTCs) exit the bloodstream to form micrometastases, they undergo its reverse process for clonal outgrowth at these metastatic sites.
References
Parola M., Pinzani M. Hepatic wound repair. Fibrogenesis Tissue Repair 2009 25; 2(1): 4.
Kalluri R. EMT: when epithelial cells decide to become mesenchymal-like cells. J Clin Invest 2009; 119(6): 1417-9. http://dx.doi.org/10.1172/JCI39675
Kalluri R, Weinberg RA. The basics of epithelialmesenchymal transition. J Clin Invest 2009; 119(6): 1420- 1428. http://dx.doi.org/10.1172/JCI39104
Forbes SJ, Parola M. Liver fibrogenic cells. Best Pract Res Clin Gastroenterol 2011; 25(2): 207-17. http://dx.doi.org/10.1016/j.bpg.2011.02.006
Acloque H, Adams MS, Fishwick K, Bronner-Fraser M, Nieto MA. Epithelial-mesenchymal transitions: the importance of changing cell state in development and disease. J Clin Invest 2009; 119(6): 1438-49. http://dx.doi.org/10.1172/JCI38019
Pinzani M. Epithelial-mesenchymal transition in chronic liver disease: fibrogenesis or escape from death? J Hepatol 2011; 55(2): 459-65. http://dx.doi.org/10.1016/j.jhep.2011.02.001
Guarino M, Tosoni A, Nebuloni M. Direct contribution of epithelium to organ fibrosis: epithelial-mesenchymal transition. Hum Pathol 2009; 40(10): 1365-76. http://dx.doi.org/10.1016/j.humpath.2009.02.020
Novo E, di Bonzo LV, Cannito S, Colombatto S, Parola M. Hepatic myofibroblasts: a heterogeneous population of multifunctional cells in liver fibrogenesis. J Biochem Cell Biol 2009; 41(11): 2089-93. http://dx.doi.org/10.1016/j.biocel.2009.03.010
Kalluri R, Neilson EG. Epithelial-mesenchymal transition and its implications for fibrosis. J Clin Invest 2003; 112(12): 1776- 84. http://dx.doi.org/10.1172/JCI200320530
Radisky DC, Kenny PA, Bissell MJ. Fibrosis and cancer: do myofibroblasts come also from epithelial cells via EMT? J Cell Biochem 2007; 101(4): 830-9. http://dx.doi.org/10.1002/jcb.21186
Rygiel KA, Robertson H, Marshall HL, Pekalski M, Zhao L, Booth TA, Jones DE, Burt AD, Kirby JA Epithelialmesenchymal transition contributes to portal tract fibrogenesis during human chronic liver disease. Lab Invest 2008; 88(2): 112-23. http://dx.doi.org/10.1038/labinvest.3700704
Li B, Zheng YW, Sano Y, Taniguchi H. Evidence for mesenchymal-epithelial transition associated with mouse hepatic stem cell differentiation. PLoS One 2011 11; 6(2): 170-92.
Kasai H, Allen JT, Mason RM, Kamimura T, Zhang Z. TGFbeta1 induces human alveolar epithelial to mesenchymal cell transition (EMT). Respir Res 2005; 6: 56. http://dx.doi.org/10.1186/1465-9921-6-56
Kaimori A, Potter J, Kaimori JY, Wang C, Mezey E, Koteish A. Transforming growth factor-beta1 induces an epithelial-tomesenchymal transition state in mouse hepatocytes in vitro. J Biol Chem 2007; 282(30): 22089-101. http://dx.doi.org/10.1074/jbc.M700998200
Lebleu VS, Taduri G, O'Connell J. et al. Origin and function of myofibroblasts in kidney fibrosis. Nature Med 2013; 19(8): 1047–1053. http://dx.doi.org/10.1038/nm.3218
Postlethwaite AE, Shigemitsu H, Kanangat S. Cellular origins of fibroblasts: possible implications for organ fibrosis in systemic sclerosis. Curr Opin Rheumatol 2004; 16(6): 733- 738. http://dx.doi.org/10.1097/01.bor.0000139310.77347.9c
Chapman HA. Epithelial-mesenchymal interactions in pulmonary fibrosis. Annu Rev Physiol 2011; 73: 413-435. http://dx.doi.org/10.1146/annurev-physiol-012110-142225
Deng YH, Pu CL, Li YC, Zhu J, Xiang C, Zhang MM, Guo CB. Analysis of biliary epithelial-mesenchymal transition in portal tract fibrogenesis in biliary atresia. Dig Dis Sci 2011; 56(3): 731-40. http://dx.doi.org/10.1007/s10620-010-1347-6
Maheswaran T, Rushbrook SM. Epithelial-mesenchymal transition and the liver: role in hepatocellular carcinoma and liver fibrosis. J Gastroenterol Hepatol 2012; 27(3): 418-20. http://dx.doi.org/10.1111/j.1440-1746.2012.07060.x
Gressner OA, Rizk MS, Kovalenko E, Weiskirchen R, Gressner AM. Changing the pathogenetic roadmap of liver fibrosis? Where did it start; where will it go? J Gastroenterol Hepatol 2008; 23(7 Pt 1): 1024-35. http://dx.doi.org/10.1111/j.1440-1746.2008.05345.x
Lee JM, Dedhar S, Kalluri R, Thompson EW. The epithelialmesenchymal transition: new insights in signaling, development, and disease. J Cell Biol 2006 27; 172(7): 973- 81. 69.
Choi SS, Diehl AM. Epithelial-to-mesenchymal transitions in the liver. Hepatology 2009; 50(6): 2007-13. http://dx.doi.org/10.1002/hep.23196
Burt A, Portmann B, Ferrell L, Mac Sween’s Pathology of the liver. 6th ed. Churchill Livingston- Elsevier 2012; 361-402.
Kim JH, Jang YS, Eom KS, Hwang YI, Kang HR, Jang SH, et al. Transforming growth factor beta1 induces epithelial-tomesenchymal transition of A549 cells. J Korean Med Sci 2007; 22: 898-904. http://dx.doi.org/10.3346/jkms.2007.22.5.898
Del Castillo G, Murillo MM, Alvarez-Barrientos A, Bertran E, Fernandez M, et al. Autocrine production of TGF-beta confers resistance to apoptosis after an epithelialmesenchymal transition process in hepatocytes: Role of EGF receptor ligands. Exp Cell Res 2006; 312: 2860-2871. http://dx.doi.org/10.1016/j.yexcr.2006.05.017
