| Literature DB >> 26267533 |
Lisa M Ooms1, Lauren C Binge1, Elizabeth M Davies1, Parvin Rahman1, James R W Conway2, Rajendra Gurung1, Daniel T Ferguson1, Antonella Papa1, Clare G Fedele1, Jessica L Vieusseux1, Ryan C Chai1, Frank Koentgen3, John T Price1, Tony Tiganis1, Paul Timpson2, Catriona A McLean4, Christina A Mitchell5.
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.Entities:
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Year: 2015 PMID： 26267533 DOI： 10.1016/j.ccell.2015.07.003
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743