E-cadherin and its downstream catenins are proteolytically cleaved in human HaCaT keratinocytes exposed to UVB.
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.
Hung
Chi-Feng
CF
School of Medicine, Fu-Jen Catholic University, Taipei County, Taiwan.
Chiang
Han-Sun
HS
Lo
Huey-Ming
HM
Jian
Jr-Shian
JS
Wu
Wen-Bin
WB
D017209:Apoptosis / Q000528:radiation effects; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D015603:Keratinocytes / Q000737:chemistry / Q000378:metabolism* / Q000528:radiation effects*; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009842:Oligopeptides / Q000494:pharmacology; D010447:Peptide Hydrolases / Q000378:metabolism; D014466:Ultraviolet Rays; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*; D051185:gamma Catenin / Q000235:genetics / Q000378:metabolism*
D015820:Cadherins; D061945:Caspase Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D009842:Oligopeptides; C110772:benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; C403753:benzyloxycarbonyl-isoleucyl-glutamyl-threonyl-aspartic acid fluoromethyl ketone; D051176:beta Catenin; D051185:gamma Catenin; D010447:Peptide Hydrolases; D020169:Caspases; D020782:Matrix Metalloproteinases