The epigenetic factor KDM2B regulates cell adhesion, small rho GTPases, actin cytoskeleton and migration in prostate cancer cells

• Published in: Biochimica et biophysica acta. Molecular cell research 2018-04, Vol.1865 (4), p.587-597
• Main Authors: Zacharopoulou, Nefeli, Tsapara, Anna, Kallergi, Galatea, Schmid, Evi, Tsichlis, Philip N., Kampranis, Sotirios C., Stournaras, Christos
• Format: Article
• Language: English
• Subjects: Actin; Actin Cytoskeleton - metabolism; Biomarkers, Tumor - metabolism; Cadherins - metabolism; Cell Adhesion - genetics; Cell Line, Tumor; Cell Movement - genetics; Enhancer of Zeste Homolog 2 Protein - metabolism; Epigenesis, Genetic; F-Box Proteins - genetics; F-Box Proteins - metabolism; Gene Expression Regulation, Neoplastic; HEK293 Cells; Humans; Jumonji Domain-Containing Histone Demethylases - genetics; Jumonji Domain-Containing Histone Demethylases - metabolism; KDM2B; Male; Migration; Models, Biological; Prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; rho GTP-Binding Proteins - metabolism; Rho-GTPases; Zo-1; Zonula Occludens-1 Protein - metabolism
• ISSN: 0167-4889; 1879-2596
• DOI: 10.1016/j.bbamcr.2018.01.009

The histone demethylase KDM2B is an epigenetic factor with oncogenic properties that is regulated by the basic fibroblasts growth factor (FGF-2). It has recently been shown that KDM2B co-operates with Polycomb Group proteins to promote cell migration and angiogenesis in tumors. In the present study we addressed the role of KDM2B in regulating actin cytoskeleton signaling, cell-cell adhesion and migration of prostate tumor cells. We report here that KDM2B is functionally expressed in DU-145 prostate cancer cells, activated by FGF-2 and regulates EZH2. KDM2B knockdown induced potent up-regulation of gene transcription and protein expression of the epithelial markers E-cadherin and ZO-1, while KDM2B overexpression down-regulated the levels of both markers, suggesting control of cell adhesion by KDM2B. RhoA and RhoB protein expression and activity were diminished upon KDM2B-knockdown and upregulated in KDM2B-overexpressing cell clones. In accordance, actin reorganization with formation of stress fibers became evident in KDM2B-overexpressing cells and abolished in the presence of the Rho inhibitor C3 transferase. DU-145 cell migration was significantly enhanced in KDM2B overexpressing cells and abolished in C3-pretreated cells. Conversely, the retardation of cell migration observed in KDM2B knockdown cells was enhanced in C3-pretreated cells. These results establish a clear functional link between the epigenetic factor KDM2B and the regulation of cell adhesion and Rho-GTPases signaling that controls actin reorganization and cell migration. [Display omitted] •KDM2B is functionally expressed in DU-145 prostate cancer cells•KDM2B controls the expression of the adhesion markers E-Cadherin and ZO-1•KDM2B regulates actin cytoskeleton organization and the expression and function of small Rho GTPases•KDM2B-induced regulation of actin/Rho GTPase signaling controls motility of DU-145 prostate cancer cells