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The Inositol Polyphosphate 5-Phosphatase PIPP regulates AKT1-dependent breast cancer growth and metastasis.

Abstract

Metastasis is the major cause of breast cancer mortality. Phosphoinositide 3-kinase (PI3K) generated PtdIns(3,4,5)P3 activates AKT, which promotes breast cancer cell proliferation and regulates migration. To date, none of the inositol polyphosphate 5-phosphatases that inhibit PI3K/AKT signaling have been reported as tumor suppressors in breast cancer. Here, we show depletion of the inositol polyphosphate 5-phosphatase PIPP (INPP5J) increases breast cancer cell transformation, but reduces cell migration and invasion. Pipp ablation accelerates oncogene-driven breast cancer tumor growth in vivo, but paradoxically reduces metastasis by regulating AKT1-dependent tumor cell migration. PIPP mRNA expression is reduced in human ER-negative breast cancers associated with reduced long-term outcome. Collectively, our findings identify PIPP as a suppressor of oncogenic PI3K/AKT signaling in breast cancer.

Type Journal
Authors Ooms, L. M.; Binge, L. C.; Davies, E. M.; Rahman, P.; Conway, J. R.; Gurung, R.; Ferguson, D. T.; Papa, A.; Fedele, C. G.; Vieusseux, J. L.; Chai, R. C.; Koentgen, F.; Price, J. T.; Tiganis, T.; Timpson, P.; McLean, C. A.; Mitchell, C. A.
Publisher Name CANCER CELL
Published Date 2015-01-01 00:00:00
Published Volume 28
Published Issue 2
Published Pages 155-169
URL http://www.ncbi.nlm.nih.gov/pubmed/26267533
Status Published in-print