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/beta-catenin interactions, endogenous E-cadherin and beta-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 beta-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. (c) 2004 Wiley-Liss, Inc.
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/beta-catenin interactions, endogenous E-cadherin and beta-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 beta-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. (c) 2004 Wiley-Liss, Inc.
Authors: Rainer Kuefer; Kathleen C Day; Celina G Kleer; Michael S Sabel; Matthias D Hofer; Sooryanarayana Varambally; Christoph S Zorn; Arul M Chinnaiyan; Mark A Rubin; Mark L Day Journal: Neoplasia Date: 2006-04 Impact factor: 5.715
Authors: Porfirio Nava; Mike G Laukoetter; Ann M Hopkins; Oskar Laur; Kirsten Gerner-Smidt; Kathleen J Green; Charles A Parkos; Asma Nusrat Journal: Mol Biol Cell Date: 2007-09-05 Impact factor: 4.138