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



: Ooms LM, Binge LC, Davies EM, Rahman P, Conway JR, Gurung R, Ferguson DT, Papa A, Fedele CG, Vieusseux JL, Chai RC, Koentgen F, Price JT, Tiganis T, Timpson P, Mitchell CA, McLean CA

: 2015

: Cancer Cell

: Cancer cell

: Cancer Cell

: 28

: 2

: 155

: 69

: 15

: 1535-6108

: 1878-3686

DOI: https://doi.org/10.1016/j.ccell.2015.07.003


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.



Last updated on 2024-26-11 at 20:45