Cancer Cell 2015 Aug 10;28(2):155-69. doi: 10.1016/j.ccell.2015.07.003.
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; McLean, CA; Mitchell, CA
Monash University, Clayton, VIC, Australia; The Kinghorn Cancer Centre and University of NSW, Darlinghurst, Australia; Ozgene Pty Ltd, Bentley, WA, Australia; Alfred Hospital, Prahran, VIC, Australia.
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.
The team at Ozgene has over two decades of experience creating customised knockout and knock-in mice for pivotal medical research globally. Over 350 scientific publications are based on research using Ozgene mice.