Cdc25A regulates matrix metalloprotease 1 through Foxo1 and mediates metastasis of breast cancer cells.

Abstract:

:Cdc25A is a cell cycle-activating phosphatase, and its overexpression in breast cancers has been shown to correlate with poor prognosis. Most recent studies related to Cdc25A and tumor progression have focused on its role in regulating cell cycle progression. However, less is known about how Cdc25A modulates the metastasis of breast cancer cells. In this study, we revealed that Cdc25A enhances Foxo1 stability by dephosphorylating Cdk2, and Foxo1 was shown to directly regulate transcription of the metastatic factor MMP1. Further studies have shown that overexpression of Cdc25A in breast cancer cells enhances metastasis, whereas its downmodulation inhibits metastasis in mouse models, and the effects of Cdc25A on breast cancer cell metastasis are independent of cell proliferation and apoptosis. Furthermore, we have demonstrated that aberrant Cdc25A in breast cancer patient samples directly correlates with the metastatic phenotype. Further insights into this critical role of Cdc25A in the metastasis of breast cancer cells and the trial of an anti-Cdc25A strategy in mouse models may reveal its therapeutic potential in prevention and treatment of breast cancer cell dissemination.

journal_name

Mol Cell Biol

authors

Feng X,Wu Z,Wu Y,Hankey W,Prior TW,Li L,Ganju RK,Shen R,Zou X

doi

10.1128/MCB.05523-11

subject

Has Abstract

pub_date

2011-08-01 00:00:00

pages

3457-71

issue

16

eissn

0270-7306

issn

1098-5549

pii

MCB.05523-11

journal_volume

31

pub_type

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