The Inositol Polyphosphate 5-Phosphatase PIPP Regulates AKT1-Dependent Breast Cancer Growth and Metastasis
Copyright policy )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.
- Monash University Australia
- The Alfred Hospital Australia
- The Kinghorn Cancer Centre Australia
- Victoria University Australia
- Garvan Institute of Medical Research Australia
Cancer Research, mice, College of Health and Biomedicine, Mice, Nude, Breast Neoplasms, tumours, Kaplan-Meier Estimate, Phosphatidylinositol 3-Kinases, shRNA, Cell Movement, Cell Line, Tumor, Animals, Humans, 1112 Oncology and Carcinogenesis, Neoplasm Metastasis, Cell Proliferation, Mice, Knockout, PyMT, Mice, Inbred BALB C, College of Education, Reverse Transcriptase Polymerase Chain Reaction, AKT, Inositol Polyphosphate 5-Phosphatases, Cell Biology, 540, Immunohistochemistry, Phosphoric Monoester Hydrolases, College of Business, Gene Expression Regulation, Neoplastic, Oncology, RNA Interference, Other, Proto-Oncogene Proteins c-akt, Signal Transduction
Cancer Research, mice, College of Health and Biomedicine, Mice, Nude, Breast Neoplasms, tumours, Kaplan-Meier Estimate, Phosphatidylinositol 3-Kinases, shRNA, Cell Movement, Cell Line, Tumor, Animals, Humans, 1112 Oncology and Carcinogenesis, Neoplasm Metastasis, Cell Proliferation, Mice, Knockout, PyMT, Mice, Inbred BALB C, College of Education, Reverse Transcriptase Polymerase Chain Reaction, AKT, Inositol Polyphosphate 5-Phosphatases, Cell Biology, 540, Immunohistochemistry, Phosphoric Monoester Hydrolases, College of Business, Gene Expression Regulation, Neoplastic, Oncology, RNA Interference, Other, Proto-Oncogene Proteins c-akt, Signal Transduction
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