N-cadherin regulates mammary tumor cell migration through Akt3 suppression

S. Chung, J. Yao, K. Suyama, S. Bajaj, X. Qian, O. D. Loudig, E. A. Eugenin, G. R. Phillips, R. B. Hazan

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

N-cadherin is a cell-cell adhesion molecule that plays a role in breast cancer metastasis. Here, we show that in vivo expression of N-cadherin in the PyMT mouse model, which enhances mammary tumor metastasis, results in selective inhibition of Akt3 expression and phosphorylation. Similarly, exogenous expression of N-cadherin in PyMT or MCF-7 mammary tumor cells enhanced cell motility and caused a dramatic reduction in Akt3 expression and phosphorylation. Moreover, knockdown of Akt3 in PyMT tumor cells increased cell motility and disrupted mammary morphogenesis, but had no effect on cell proliferation. Conversely, overexpression of wild-type Akt3 in PyMT-N-cadherin cells inhibited cell motility promoted by N-cadherin. Taken altogether, these findings demonstrate that N-cadherin suppresses Akt3 to promote cell motility and highlight the intricate regulation of Akt isoforms by N-cadherin during metastasis.

Original languageEnglish (US)
Pages (from-to)422-430
Number of pages9
JournalOncogene
Volume32
Issue number4
DOIs
Publication statusPublished - Jan 24 2013

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Keywords

  • Akt isoforms
  • Akt3
  • adhesion
  • breast cancer
  • motility

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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