EBP50 regulates senescence and focal adhesion in endometrial carcinoma

Abstract

Ezrin-radixin-moesin (ERM)-binding phosphoprotein 50 (EBP50) is a multifunctional scaffold protein that is highly expressed in polarized epithelial cells. Here, we focused on the functional roles of EBP50 in endometrial carcinoma (Em Ca). We analyzed immunohistochemical sections from 121 Em Ca and 30 normal samples. We also characterized EBP50 overexpression or knockout (KO) Em Ca cell lines. High levels of membranous (Me) EBP50 expression were observed in endometrial tissues from normal menstrual cycles, in contrast to the transient upregulation of cytoplasmic (Cyt) EBP50 in tissues in the proliferative phase; this was probably in response to estrogenic effects. There was a significant stepwise reduction of Me-EBP50 expression from grade (G) 1 to G3 Em Cas, which was consistent with the loss of glandular structures. Conversely, Cyt-EBP50 levels increased with in the higher tumor grades. Low Me-EBP50 expression was significantly associated with tumor lymphovascular invasion and short overall survival. Whereas EBP50 KO led to senescence and reduced proliferation and motility, overexpression elicited the opposite phenotypes. Moreover, the number of focal adhesions (FAs), which mediate cell migration, was significantly increased in EBP50 overexpressing cells but decreased in the KO cells. In conclusion, Me- and/or Cyt-EBP50 expression contributes to acceleration of cell motility through enhancement of FA formation, and inhibits senescence to promote cytokinesis. Together, these effects contribute to Em Ca aggressiveness.