Journal of Cell Science, Vol 112, Issue 1 127-135, Copyright © 1999 by Company of Biologists

JOURNAL ARTICLES

Inhibition of adhesion and induction of epithelial cell invasion by HAV-containing E-cadherin-specific peptides

V Noe, J Willems, J Vandekerckhove, FV Roy, E Bruyneel and M Mareel
Laboratory of Experimental Cancerology, UZG, B-9000 Ghent, Belgium.

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.

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