Epithelial-to-mesenchymal transition

Abbreviations AFP, a-fetoprotein CK, cytokeratin ECM, extracellular matrix EMT, epithelial to mesenchymal transition HCC, hepatocellular carcinoma HNF, hepatocyte nuclear factor, HSC, hepatic stellate cell MFB, myofibroblast M2-PK, M2-pyruvate kinase PDGF, platelet-derived growth factor TGF, transforming growth factor. 

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Fig. 1. Microenvironmental factors and the invasive process. The primary tumor is a heterogeneous mix of cell populations, further diversified by gradients of blood-borne nutrients, oxygen, and drugs. Hypoxia contributes to treatment resistance, upregulates pro-angiogenic and pro-invasive molecules, and helps to maintain cancer stem-like cell populations. Tumor cells may undergo epithelial-to-mesenchymal transition (EMT), enter blood vessels, and disseminate to distant sites where they extravasate, invade, and colonize the tissues. Once established, the cells may undergo the reverse program (mesen-chymal-to-epithelial transition, MET) and proliferate to form metastases, the major reason for treatment failure.

Chung CH, Parker JS, Ely K et al. Gene expression profiles identify epithelial-to-mesenchymal transition and activation of nuclear factor-Kb signaling as characteristics of a high-risk head and neck squamous cell carcinoma. CuwcerRe 2006 66 8210-8218. 

In the course of cancer development, cells undergo changes that resemble epithelial to mesenchymal transitions that occur during embryology. Stimulation of HA synthesis is sufficient in some model systems to promote such transitions in apparently normal epithelial cell cultures. This transition can occur by transfection and over-expression of HAS2 [125]. 

Yanez M6 M, Lara-Pezzi E, Selgas R, et al. Peritoneal Dialysis and Epithelial-to-Mesenchymal Transition of Mesothelial Cells. N Engl J Med 2003 348 403-13. 

In some DAs the hallmarks of ductal differentiation may be lacking. Such cases are classified as undifferentiated carcinoma.In some, epithelial-to-mesenchymal transition can be so complete that the tumor may resemble sarcomas (i.e., sarcomatoid carcinoma)and only after adjunct studies such as immunohistochemistry can the ductal nature of the tumor be elucidated. ... 

Tse JC, Kalluri R. Mechanisms of metastasis epithelial-to-mesenchymal transition and contribution of tumor microenvironment. J Cell Biochem 2007 101 816-829. 

M. Tania, M. Khan, and J. Fu, Epithelial to mesenchymal transition inducing transcription factors and metastatic cancer. Tumour Biol, (2014). 

Yee DS, Tang Y, Li X, Liu Z, Guo Y, Ghaffar S, McQueen P, Atreya D, Xie J, Simoneau AR, Hoang BH, Zi X. The Wnt inhibitory factor 1 restoration in prostate cancer cells was associated with reduced tumor growth, decreased capacity of cell migration and invasion and a reversal of epithelial to mesenchymal transition. Mol Cancer. 2010 23(9) 162. 

Rangel MC, Karasawa H, Castro NP, Nagaoka T, Salomon DS, Bianco C. Role of Cripto-1 during epithelial-to-mesenchymal transition in development and ermcer. Am J Pathol. 2012 189 2188-200. 

Shah PP, Kakatr SS. Pituitary tumor transforming gene induces epithelial to mesenchymal transition of Twist, Snail, Slug, and E-cadherin. Cancer Lett. 2011 311 66-76. 

Unno J, Satoh K, Hirota M, Kanno A, Hamada S, Masamune A, Tsukamoto N, Motoi F, Egawa S, Unno M, Horiii A, Shimosegawa T. liv-1 enhances the aggressive phenotypes through the induction of epithelial to mesenchymal transition in human pancreatic carcinoma cells. Int J Oncol. 2009 35 813-21. 

Chua HL, Bhat-Nakashatri P, Clare SE, MOTiiniya A, Badve S, Nakshatri H. NF-kappaB represses E-cadherin expression and enhances epithelial to mesenchymal transition of mammary epithelial cells potential involvement of ZEB-1 and ZEB-2. Oncogene. 2007 26 711-24. 

Moes M, Le Bechec A, Crespo I, Laurini C, Halavalyl A, Vetter G, Del Sol A, Friederich E. A novel network integrating a miRNA-203/SNAll fedback loop which regulates epithelial to mesenchymal transition. PLoS One. 2012 7(4) e35440. 

Luo, Li W, Liao H. HMGA2 induees epithelial-to-mesenchymal transition in human hepatocellular carcinoma cells. Oncol Lett 2013 5L1353-1356. 

Sun CK, Ng KT, Lim ZX, Cheng Q, Lo CM, Poon RT, Man K, Wong N, Fan ST. 2011. Prohne-rich tyrosine kinase 2 (Pyk2) promotes cell motility of hepatocellular carcinoma through induction of epithelial to mesenchymal transition. PLoS One 6(4) el8878. 

Finally, inhibition of protein deacetylation with histone deacetylase (HDAC) inhibitors has shown promise in preclinical models of cardiovascular and renal disease, including myocyte hypertrophy, fibrosis, inflammation and epithelial-to-mesenchymal transition." ... 

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