1. ¹Department of Oral Biology, University of Nebraska Medical Center, Omaha, NE, USA
2. ²Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
3. ³Eppley Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA
4. ⁴Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, USA

Correspondence: Professor MJ Wheelock, The University of Nebraska Medical Center, 987696 Nebraska Medical Center, Omaha, NE 68198-7696, USA. E-mail: mwheelock@unmc.edu

⁵These authors contributed equally to this work.

Received 2 June 2005; Revised 8 December 2005; Accepted 9 December 2005; Published online 19 June 2006.

Abstract

Cadherin cell–cell adhesion proteins play an important role in modulating the behavior of tumor cells. E-cadherin serves as a suppressor of tumor cell invasion, and when tumor cells turn on the expression of a non-epithelial cadherin, they often express less E-cadherin, enhancing the tumorigenic phenotype of the cells. Here, we show that when A431 cells are forced to express R-cadherin, they dramatically downregulate the expression of endogenous E- and P-cadherin. In addition, we show that this downregulation is owing to increased turnover of the endogenous cadherins via clathrin-dependent endocytosis. p120^ctn binds to the juxtamembrane domain of classical cadherins and has been proposed to regulate cadherin adhesive activity. One way p120^ctn may accomplish this is to serve as a rheostat to regulate the levels of cadherin. Here, we show that the degradation of E-cadherin in response to expression of R-cadherin is owing to competition for p120^ctn.