TY - JOUR
T1 - The inositol polyphosphate 5-Phosphatase PIPP regulates AKT1-Dependent breast cancer growth and metastasis
AU - Ooms, Lisa M
AU - Binge, Lauren C
AU - Davies, Elizabeth M
AU - Rahman, Parvin
AU - Conway, James R W
AU - Gurung, Rajendra
AU - Ferguson, Daniel T
AU - Papa, Antonella
AU - Fedele, Clare G
AU - Vieusseux, Jessica L
AU - Chai, Ryan C C
AU - Koentgen, Frank
AU - Price, John T
AU - Tiganis, Tony
AU - Timpson, Paul
AU - McLean, Catriona A
AU - Mitchell, Christina Anne
PY - 2015/8/10
Y1 - 2015/8/10
N2 - 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.
AB - 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.
UR - http://www.ncbi.nlm.nih.gov/pubmed/26267533
U2 - 10.1016/j.ccell.2015.07.003
DO - 10.1016/j.ccell.2015.07.003
M3 - Article
VL - 28
SP - 155
EP - 169
JO - Cancer Cell
JF - Cancer Cell
SN - 1535-6108
IS - 2
ER -
