PUTATIVE MECHANISM THROUGH WHICH N-CADHERIN-MEDIATED CELL CONTACT MAINTAINS CALCIUM HOMEOSTASIS AND THEREBY PREVENTS OVARIAN-CELLS FROM UNDERGOING APOPTOSIS

To date most of the studies involving the maintenance of ovarian cell viability have focused on the endocrine, paracrine, and autocrine fact ors that inhibit these cells from undergoing programmed cell death or apoptosis. Recently, studies have demonstrated that cell contact also prevents ovarian cells from dying via an apoptotic mechanism. In this commentary, the role that hemophilic binding of the cell adhesion mole cule, N-cadherin, plays in maintaining ovarian cell viability is prese nted. These studies showed that N-cadherin hemophilic binding (1) is p art of the mechanism through which cell contact maintains cell viabili ty, (2) results in the activation (i.e. tyrosine phosphorylation) oi t he fibroblast growth factor (FGF) receptor, and (3) prevents a sustain ed elevation in intracellular free calcium ([Ca2+](i)) which triggers apoptosis. These studies also revealed that hepatocyte growth factor ( HGF), also known as scatter factor (SF), disrupts cell contact, which leads to a sustained increase in [Ca2+](i) levels and ultimately to ce ll death. Based on these studies, this commentary presents a putative mechanism that relates the cellular and molecular mechanism through wh ich basic FGF, N-cadherin, and HGF/SF interact to regulate [Ca2+](i) l evels and ultimately ovarian cell survival. (C) 1997 Elsevier Science Inc.