Inhibition of adhesion and induction of epithelial cell invasion by HAV-containing E-cadherin-specific peptides.
The E-cadherin/catenin complex, an organizer of epithelial structure and function, is disturbed in invasive cancer. The HAV (histidine alanine valine) sequence in the first extracellular domain of E-cadherin is crucial for homophilic interactions between cadherins. We report that specific peptides containing an HAV sequence interfere with the functions of the E-cadherin/catenin complex. Cells either expressing specific cadherins or not were challenged with both cadherin and noncadherin peptides comprising a central HAV sequence. Specific E-cadherin peptides inhibited cell aggregation, disturbed the epithelial morphotype and were able to stimulate invasion of cells expressing E-cadherins. Conditioned medium, containing E-cadherin fragments, also stimulated invasion in contrast to conditioned medium from which the E-cadherin fragments were removed. Our studies show that E-cadherin functions are inhibited by homologous proteolytic HAV-containing fragments that are released in an autocrine manner and subsequently inhibit the E-cadherin/catenin complex. In this way such cadherin fragments may induce and support cancer invasion.
Noë
V
V
Laboratory of Experimental Cancerology, UZG, B-9000 Ghent, Belgium.
Willems
J
J
Vandekerckhove
J
J
Roy
F V
FV
Bruyneel
E
E
Mareel
M
M
D000409:Alanine / Q000737:chemistry*; D000595:Amino Acid Sequence; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002449:Cell Aggregation / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002642:Chick Embryo; D003094:Collagen / Q000378:metabolism; D006224:Cricetinae; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004285:Dogs; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006639:Histidine / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009206:Myocardium / Q000166:cytology; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology; D014633:Valine / Q000737:chemistry*
D015820:Cadherins; D017077:Culture Media, Conditioned; D009842:Oligopeptides; D006639:Histidine; D003094:Collagen; D014633:Valine; D000409:Alanine