Gamma secretase inhibitor impairs epithelial-to-mesenchymal transition induced by TGF-β in ovarian tumor cell lines.

IRUSTA G; ACCIALINI P; PAZOS C; TESONE M; BECHIS A; PARBORELL F; ABRAMOVICH D

MOLECULAR AND CELLULAR ENDOCRINOLOGY.

ELSEVIER IRELAND LTD

Lugar: Amsterdam; Año: 2017 vol. 440 p. 125 - 137

0303-7207

Ovarian cancer is characterized by being highly metastatic, a feature thatrepresents the main cause of failure of the treatment. This study investigatedthe effects of γ-secretase inhibition on the TGF-β-induced epithelial-mesenchymaltransition (EMT) process in ovarian cancer cell lines. SKOV3 cells incubated inthe presence of TGF-β showed morphological and biochemical changes related toEMT, which were blocked by co-stimulation with TGF-β and the γ-secretaseinhibitor DAPT. In SKOV3 and IGROV1 cells, the co-stimulation blocked thecadherin switch and the increase in the transcription factors Snail, Slug, Twist and Zeb1 induced by TGF-β. DAPT impaired the translocation of phospho-β-cateninto the inner cell compartment observed in TGF-β-treated cells, but was not ableto block the induction at protein level induced by TGF-β. Moreover, the inhibitorblocked the increased cell migration and invasiveness ability of both cell lines induced by TGF-β. Notch target genes (Hes1 and Hey1) were induced by TGF-β,decreased by DAPT treatment and remained low in the presence of both stimuli.However, DAPT alone caused no effects on most of the parameters analyzed. Theseresults demonstrate that the γ-secretase inhibitor used in this study exerted ablockade on TGF-β-induced EMT in ovarian cancer cells.Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.DOI: 10.1016/j.mce.2016.11.025 PMID: 27908834