The Inositol Polyphosphate 5-Phosphatase PIPP regulates AKT1-dependent breast cancer growth and metastasis.
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.
|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|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/pubmed/26267533|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/13051|