Truncated E-cadherin potentiates cell death in prostate epithelial cells

Abstract

BACKGROUND E-cadherin, a fundamental component of the adherens junction, is known to mediate aggregation-dependent cell survival. We have previously identified a novel, calpain-dependent proteolytic cleavage of E-cadherin that resulted in the generation of a stable 100-kDa E-cadherin fragment (E-cad 100 ) in prostate epithelial cells in response to cell death stimuli. We postulated that the E-cad 100 fragment may play a role in abrogating survival of LNCaP cells following induction of apoptosis. METHODS Wild-type E-cadherin and E-cad 100 were engineered, tagged with GFP, and stably expressed in LNCaP cells. These cell lines were characterized for E-cadherin-GFP/Β-catenin interactions, endogenous E-cadherin and Β-catenin expression, and sensitivity to apoptosis induced by PKC activation. RESULTS E-cad 100 -GFP demonstrated a punctuate expression pattern, in contrast to E-cad 120 -GFP, which was membrane-localized. E-cad 100 -GFP, unlike E-cad 120 -GFP, failed to bind to and co-localize with Β-catenin. Transient or stable overexpression of E-cad 100 resulted in the downregulation of endogenous E-cadherin expression at the cell membrane. Activation of PKC in LNCaP cells which overexpressed E-cad 100 potentiated cell death. CONCLUSIONS Truncated E-cadherin may play a role in the regulation of endogenous E-cadherin expression and epithelial cell survival. © 2004 Wiley-Liss, Inc.