N-cadherin regulates mammary tumor cell migration through Akt3 suppression.

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.

journal_name

Oncogene

journal_title

Oncogene

authors

Chung S,Yao J,Suyama K,Bajaj S,Qian X,Loudig OD,Eugenin EA,Phillips GR,Hazan RB

doi

10.1038/onc.2012.65

subject

Has Abstract

pub_date

2013-01-24 00:00:00

pages

422-30

issue

4

eissn

0950-9232

issn

1476-5594

pii

onc201265

journal_volume

32

pub_type

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