E-cadherin and its downstream catenins are proteolytically cleaved in human HaCaT keratinocytes exposed to UVB

Exp Dermatol. 2006 Apr;15(4):315-21. doi: 10.1111/j.0906-6705.2006.00411.x.

Abstract

It has been reported that ultraviolet B (UVB) irradiation causes the loss of E-cadherin of melanocytes, leading them to escape from neighboring keratinocytes during melanoma development. However, little has been paid on its effect on E-cadherin of keratinocytes. In the present study we therefore focus on whether UVB affects expression of E-cadherin-catenin complex in human HaCaT keratinocytes. We found that E-cadherin, beta-, and gamma-catenin but not alpha-catenin were proteolytically cleaved in UVB-irradiated HaCaT keratinocytes. The effect was only observed in keratinocyte undergoing apoptosis. Cleavage of beta- and gamma-catenin was fully abolished by caspase-3 and caspase-8 inhibitors, whereas cleavage of E-cadherin was inhibited by neither caspase nor metalloproteinase inhibitors. Functional analysis showed that the cleavage resulted in the disruption of the physical association between E-cadherin and catenins, indicating that E-cadherin signaling was compromised in UVB-irradiated HaCaT keratinocytes. Because E-cadherin in keratinocytes plays important roles in mediating cell-cell adhesion in epidermis of skin, the loss of E-cadherin and signaling components in keratinocytes may lead to the disruption of skin integrity after UVB exposure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / radiation effects
  • Blotting, Western
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Caspase Inhibitors
  • Caspases / metabolism
  • Cell Line
  • Flow Cytometry
  • Gene Expression Regulation
  • Humans
  • Keratinocytes / chemistry
  • Keratinocytes / metabolism*
  • Keratinocytes / radiation effects*
  • Matrix Metalloproteinase Inhibitors
  • Matrix Metalloproteinases / metabolism
  • Microscopy, Fluorescence
  • Oligopeptides / pharmacology
  • Peptide Hydrolases / metabolism
  • Ultraviolet Rays*
  • beta Catenin / genetics
  • beta Catenin / metabolism*
  • gamma Catenin / genetics
  • gamma Catenin / metabolism*

Substances

  • Cadherins
  • Caspase Inhibitors
  • Matrix Metalloproteinase Inhibitors
  • Oligopeptides
  • benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone
  • benzyloxycarbonyl-isoleucyl-glutamyl-threonyl-aspartic acid fluoromethyl ketone
  • beta Catenin
  • gamma Catenin
  • Peptide Hydrolases
  • Caspases
  • Matrix Metalloproteinases