Expression of inappropriate cadherins by epithelial tumor cells promotes endocytosis and degradation of E-cadherin via competition for p120ctn

M. Maeda, E. Johnson, S. H. Mandal, K. R. Lawson, S. A. Keim, R. A. Svoboda, Steven H Caplan, James K Wahl, M. J. Wheelock, Keith R Johnson

Research output: Contribution to journalArticle

44 Citations (Scopus)

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 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 p120ctn.

Original languageEnglish (US)
Pages (from-to)4595-4604
Number of pages10
JournalOncogene
Volume25
Issue number33
DOIs
StatePublished - Aug 3 2006

Fingerprint

Cadherins
Endocytosis
Epithelial Cells
Neoplasms
Down-Regulation
delta catenin
Clathrin
Cell Adhesion
Adhesives
Phenotype

Keywords

  • Cadherin
  • Endocytosis
  • p120

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Expression of inappropriate cadherins by epithelial tumor cells promotes endocytosis and degradation of E-cadherin via competition for p120ctn. / Maeda, M.; Johnson, E.; Mandal, S. H.; Lawson, K. R.; Keim, S. A.; Svoboda, R. A.; Caplan, Steven H; Wahl, James K; Wheelock, M. J.; Johnson, Keith R.

In: Oncogene, Vol. 25, No. 33, 03.08.2006, p. 4595-4604.

Research output: Contribution to journalArticle

Maeda, M. ; Johnson, E. ; Mandal, S. H. ; Lawson, K. R. ; Keim, S. A. ; Svoboda, R. A. ; Caplan, Steven H ; Wahl, James K ; Wheelock, M. J. ; Johnson, Keith R. / Expression of inappropriate cadherins by epithelial tumor cells promotes endocytosis and degradation of E-cadherin via competition for p120ctn. In: Oncogene. 2006 ; Vol. 25, No. 33. pp. 4595-4604.
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