AbstractBACKGROUNDE‐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‐cad100) in prostate epithelial cells in response to cell death stimuli. We postulated that the E‐cad100 fragment may play a role in abrogating survival of LNCaP cells following induction of apoptosis.METHODSWild‐type E‐cadherin and E‐cad100 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.RESULTSE‐cad100‐GFP demonstrated a punctuate expression pattern, in contrast to E‐cad120‐GFP, which was membrane‐localized. E‐cad100‐GFP, unlike E‐cad120‐GFP, failed to bind to and co‐localize with β‐catenin. Transient or stable overexpression of E‐cad100 resulted in the downregulation of endogenous E‐cadherin expression at the cell membrane. Activation of PKC in LNCaP cells which overexpressed E‐cad100 potentiated cell death.CONCLUSIONSTruncated E‐cadherin may play a role in the regulation of endogenous E‐cadherin expression and epithelial cell survival. © 2004 Wiley‐Liss, Inc.