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 R W Conway, Rajendra Gurung, Daniel T Ferguson, Antonella Papa, Clare G Fedele, Jessica L Vieusseux, Ryan C C Chai, Frank Koentgen, John T Price, Tony Tiganis, Paul Timpson, Catriona A McLean, Christina Anne Mitchell

Research output: Contribution to journalArticleResearchpeer-review

63 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)155-169
Number of pages15
JournalCancer Cell
Volume28
Issue number2
DOIs
Publication statusPublished - 10 Aug 2015

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