Journal article

FOXO3a Promotes Tumor Cell Invasion through the Induction of Matrix Metalloproteinases

Peter Storz, Heike Doeppler, John A Copland, Kaylene J Simpson, Alex Toker

MOLECULAR AND CELLULAR BIOLOGY | AMER SOC MICROBIOLOGY | Published : 2009

Abstract

The role of the Forkhead transcription factor FOXO3a in processes that promote tumor metastasis is poorly defined. Here, we show that depletion of FOXO3a from cancer cells leads to decreased tumor size specifically due to attenuated invasive migration. During tumor progression, an increase in tumor mass is concomitant with serum deprivation prior to tumor angiogenesis. We show that nuclear retention of FOXO3a due to serum starvation results in greatly increased cancer cell invasion. Exploration of the mechanism by which FOXO3a promotes invasive migration revealed that it induces the expression of matrix metalloproteinase 9 (MMP-9) and MMP-13, both of which have been causally linked to the in..

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University of Melbourne Researchers

Grants

Awarded by Florida Department of Health, Bankhead-Coley Program


Awarded by Department of Defense


Awarded by National Institutes of Health


Awarded by NATIONAL CANCER INSTITUTE


Funding Acknowledgements

This work was supported by grants from the Florida Department of Health, Bankhead-Coley Program (to P. S., grant FLA07BN-08), Department of Defense (to K.J.S., grant W81XH-04-1-0360), and the National Institutes of Health (to A. T., grants NCI-R01CA075134 and R01CA122099; to J.A.C., grant NCI-R01CA104505).