TY - JOUR
T1 - The epigenetic factor KDM2B regulates cell adhesion, small rho GTPases, actin cytoskeleton and migration in prostate cancer cells
AU - Zacharopoulou, Nefeli
AU - Tsapara, Anna
AU - Kallergi, Galatea
AU - Schmid, Evi
AU - Tsichlis, Philip N
AU - Kampranis, Sotirios C
AU - Stournaras, Christos
N1 - Copyright © 2018 Elsevier B.V. All rights reserved.
PY - 2018/4
Y1 - 2018/4
N2 - 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.
AB - 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.
KW - Actin Cytoskeleton/metabolism
KW - Biomarkers, Tumor/metabolism
KW - Cadherins/metabolism
KW - Cell Adhesion/genetics
KW - Cell Line, Tumor
KW - Cell Movement/genetics
KW - Enhancer of Zeste Homolog 2 Protein/metabolism
KW - Epigenesis, Genetic
KW - F-Box Proteins/genetics
KW - Gene Expression Regulation, Neoplastic
KW - HEK293 Cells
KW - Humans
KW - Jumonji Domain-Containing Histone Demethylases/genetics
KW - Male
KW - Models, Biological
KW - Prostatic Neoplasms/genetics
KW - Zonula Occludens-1 Protein/metabolism
KW - rho GTP-Binding Proteins/metabolism
U2 - 10.1016/j.bbamcr.2018.01.009
DO - 10.1016/j.bbamcr.2018.01.009
M3 - Journal article
C2 - 29408056
SN - 0167-4889
VL - 1865
SP - 587
EP - 597
JO - B B A - Molecular Cell Research
JF - B B A - Molecular Cell Research
IS - 4
ER -
