A core function for p120-catenin in cadherin turnover

doi:10.1083/jcb.200307111

Published 10 November 2003. doi:10.1083/jcb.200307111

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© The Rockefeller University Press, 0021-9525/2003/11/525 $8.00
The Journal of Cell Biology, Volume 163, Number 3, 525-534

Article

A core function for p120-catenin in cadherin turnover

Michael A. Davis, Renee C. Ireton and Albert B. Reynolds

Department of Cancer Biology, Vanderbilt University, Nashville, TN 37232

Address correspondence to Albert B. Reynolds, Dept. of Cancer Biology, 771 PRB, 2220 Pierce Ave., Nashville, TN 37232-6840. Tel.: (615) 343-9532. Fax: (615) 936-6399. email: al.reynolds{at}mcmail.vanderbilt.edu

p120-catenin stabilizes epithelial cadherin (E-cadherin) inSW48 cells, but the mechanism has not been established. Here,we show that p120 acts at the cell surface to control cadherinturnover, thereby regulating cadherin levels. p120 knockdownby siRNA expression resulted in dose-dependent elimination ofepithelial, placental, neuronal, and vascular endothelial cadherins,and complete loss of cell–cell adhesion. ARVCF and ${delta}$ -cateninwere functionally redundant, suggesting that proper cadherin-dependentadhesion requires the presence of at least one p120 family member.The data reveal a core function of p120 in cadherin complexes,and strongly predict a dose-dependent loss of E-cadherin intumors that partially or completely down-regulate p120.

Key Words: tumor suppressor; p120-catenin; cell adhesion; tumor progression; metastasis

M.A. Davis and R.C. Ireton contributed equally to this paper.

Abbreviations used in this paper: E-cadherin, epithelial cadherin;h siRNA, human small interfering RNA; HUAEC, human umbilicalaortic endothelial cells; m siRNA, murine small interferingRNA; N-cadherin, neuronal cadherin; p120, p120-catenin; P-cadherin,placental cadherin; pRS, pRetroSuper; siRNA, small interferingRNA; VE-cadherin, vascular endothelial cadherin.

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