Hic-5 regulates epithelial to mesenchymal transition in ovarian cancer cells in a TGFβ1-independent manner
Year: 2017
Type: article
Abstract: The molecular basis of epithelial ovarian cancer (EOC) dissemination is still poorly understood.We have previously identified the hydrogen peroxide-inducible clone-5 (Hic-5) gene as hypomethylated in high-grade (HG) serous EOC tumors, compared to normal ovarian tissues.Hic-5 is a focal adhesion scaffold protein and has been primarily studied for its role as a key mediator of TGF-β-induced epithelialto-mesenchymal transition (EMT) in epithelial cells of both normal and malignant origin; however, its role in EOC has been never investigated.Here we demonstrate that Hic-5 is overexpressed in advanced EOC, and that Hic-5 is upregulated upon TGFβ1 treatment in the EOC cell line with epithelial morphology (A2780s), associated with EMT induction.However, ectopic expression of Hic-5 in A2780s cells induces EMT independently of TGFβ1, accompanied with enhancement of cellular proliferation rate and migratory/invasive capacity and increased resistance to chemotherapeutic drugs.Moreover, Hic-5 knockdown in the EOC cells with mesenchymal morphology (SKOV3) was accompanied by induction of mesenchymalto-epithelial transition (MET), followed by a reduction of their proliferative, migratory/ invasive capacity, and increased drugs sensitivity in vitro, as well as enhanced tumor cell colonization and metastatic growth in vivo.The modulation of Hic-5 expression in EOC cells resulted in altered regulation of numerous EMT-related canonical pathways and was indicative for a possible role of Hic-5 in controlling EMT through a RhoA/ ROCK mediated mechanism.To our knowledge, this is the first report examining the role of Hic-5 in EOC, and its role in maintaining the mesenchymal phenotype of EOC cells independently of exogenous TGFβ1 treatment.
Source: Oncotarget
Language: English
Topic: Cancer Cells and Metastasis
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W2742004115