Truncated E-cadherin potentiates cell death in prostate epithelial cells

Prostate. 2005 May 15;63(3):259-68. doi: 10.1002/pros.20179.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Apoptosis / drug effects*
  • Cadherins / chemistry
  • Cadherins / genetics
  • Cadherins / physiology*
  • Calpain / metabolism
  • Cell Line
  • Cell Membrane / chemistry
  • Cytoskeletal Proteins / genetics
  • Enzyme Activation
  • Epithelial Cells / chemistry
  • Epithelial Cells / cytology*
  • Gene Expression
  • Green Fluorescent Proteins / genetics
  • Humans
  • Male
  • Molecular Sequence Data
  • Peptide Fragments / genetics
  • Peptide Fragments / physiology*
  • Prostate / cytology*
  • Protein Kinase C / metabolism
  • Recombinant Fusion Proteins
  • Trans-Activators / genetics
  • Transfection
  • beta Catenin


  • CTNNB1 protein, human
  • Cadherins
  • Cytoskeletal Proteins
  • Peptide Fragments
  • Recombinant Fusion Proteins
  • Trans-Activators
  • beta Catenin
  • Green Fluorescent Proteins
  • Protein Kinase C
  • Calpain