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- Title
Expression of inappropriate cadherins by epithelial tumor cells promotes endocytosis and degradation of E-cadherin via competition for p120<sup>ctn</sup>.
- Authors
Maeda, M.; Johnson, E.; Mandal, S. H.; Lawson, K. R.; Keim, S. A.; Svoboda, R. A.; Caplan, S.; Wahl, J. K.; Wheelock, M. J.; Johnson, K. R.
- 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. p120ctn binds to the juxtamembrane domain of classical cadherins and has been proposed to regulate cadherin adhesive activity. One way p120ctn 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 p120ctn.Oncogene (2006) 25, 4595–4604. doi:10.1038/sj.onc.1209396; published online 19 June 2006
- Subjects
CADHERINS; CELL adhesion molecules; ENDOCYTOSIS; CELL physiology; CYTOSKELETON; EPITHELIAL cells; TUMORS
- Publication
Oncogene, 2006, Vol 25, Issue 33, p4595
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1209396