Journal article

The Inositol Polyphosphate 5-Phosphatase PIPP Regulates AKT1-Dependent Breast Cancer Growth and Metastasis

Lisa M Ooms, Lauren C Binge, Elizabeth M Davies, Parvin Rahman, James RW Conway, Rajendra Gurung, Daniel T Ferguson, Antonella Papa, Clare G Fedele, Jessica L Vieusseux, Ryan C Chai, Frank Koentgen, John T Price, Tony Tiganis, Paul Timpson, Catriona A McLean, Christina A Mitchell

CANCER CELL | CELL PRESS | Published : 2015

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 ex..

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