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
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..View full abstract
Awarded by NHMRC
This work was supported by a grant from the NHMRC (APP1010430). This study utilized the Australian Phenomics Network Histopathology and Organ Pathology Service, University of Melbourne and the Monash Micro Imaging Facility, Monash University, Victoria, Australia. We thank Roger Daly, Jennifer Dyson, and Jane Visvader for helpful discussions and advice.