N-cadherin regulates mammary tumor cell migration through Akt3 suppression

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

Research output: Contribution to journalArticle

32 Citations (Scopus)

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
StatePublished - Jan 24 2013

Fingerprint

Cadherins
Cell Movement
Breast Neoplasms
Neoplasm Metastasis
Phosphorylation
Cell Adhesion Molecules
Morphogenesis
Protein Isoforms
Breast
Cell Proliferation
Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

N-cadherin regulates mammary tumor cell migration through Akt3 suppression. / Chung, S.; Yao, J.; Suyama, Kimita; Bajaj, S.; Qian, X.; Loudig, O. D.; Eugenin, E. A.; Phillips, G. R.; Hazan, Rachel.

In: Oncogene, Vol. 32, No. 4, 24.01.2013, p. 422-430.

Research output: Contribution to journalArticle

Chung, S, Yao, J, Suyama, K, Bajaj, S, Qian, X, Loudig, OD, Eugenin, EA, Phillips, GR & Hazan, R 2013, 'N-cadherin regulates mammary tumor cell migration through Akt3 suppression', Oncogene, vol. 32, no. 4, pp. 422-430. https://doi.org/10.1038/onc.2012.65
Chung, S. ; Yao, J. ; Suyama, Kimita ; Bajaj, S. ; Qian, X. ; Loudig, O. D. ; Eugenin, E. A. ; Phillips, G. R. ; Hazan, Rachel. / N-cadherin regulates mammary tumor cell migration through Akt3 suppression. In: Oncogene. 2013 ; Vol. 32, No. 4. pp. 422-430.
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