AZGP1 is a tumor suppressor in pancreatic cancer inducing mesenchymal-to-epithelial transdifferentiation by inhibiting TGF-β-mediated ERK signaling.

Kong, B და Michalski, C W და Hong, X და Valkovskaya, N და Rieder, S და Abiatari, Ivane და Streit, S და Erkan, M და Esposito, I და Friess, H და Kleeff, J (2010) AZGP1 is a tumor suppressor in pancreatic cancer inducing mesenchymal-to-epithelial transdifferentiation by inhibiting TGF-β-mediated ERK signaling. Oncogene, 29 (37). С. 5146-58. ISSN 1476-5594

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რეზიუმე

Epithelial-to-mesenchymal transdifferentiation (EMT) mediated by transforming growth factor-β (TGF-β) signaling leads to aggressive cancer progression. In this study, we identified zinc-α2-glycoprotein (AZGP1, ZAG) as a tumor suppressor in pancreatic ductal adenocarcinoma whose expression is lost due to histone deacetylation. In vitro, ZAG silencing strikingly increased invasiveness of pancreatic cancer cells accompanied by the induction of a mesenchymal phenotype. Expression analysis of a set of EMT markers showed an increase in the expression of mesenchymal markers (vimentin (VIM) and integrin-α5) and a concomitant reduction in the expression of epithelial markers (cadherin 1 (CDH1), desmoplakin and keratin-19). Blockade of endogenous TGF-β signaling inhibited these morphological changes and the downregulation of CDH1, as elicited by ZAG silencing. In a ZAG-negative cell line, human recombinant ZAG (rZAG) specifically inhibited exogenous TGF-β-mediated tumor cell invasion and VIM expression. Furthermore, rZAG blocked TGF-β-mediated ERK2 phosphorylation. PCR array analysis revealed that ZAG-induced epithelial transdifferentiation was accompanied by a series of concerted cellular events including a shift in the energy metabolism and prosurvival signals. Thus, epigenetically regulated ZAG is a novel tumor suppressor essential for maintaining an epithelial phenotype.

ობიექტის ტიპი:	სტატია
თემატიკა:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
განმათავსებელი მომხმარებელი:	Dr Ivane Abiatari
განთავსების თარიღი:	30 აპრილი 2015 05:25
ბოლო ცვლილება:	30 აპრილი 2015 05:25
URI:	http://eprints.iliauni.edu.ge/id/eprint/2219

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