AI Article Synopsis
- Metastasis is the leading cause of breast cancer deaths, and the PI3K/AKT signaling pathway plays a key role in cancer cell growth and movement.
- The study reveals that lowering levels of the enzyme PIPP (INPP5J) boosts breast cancer cell transformation but surprisingly decreases their ability to migrate and invade.
- Reduced expression of PIPP is linked to poor long-term outcomes in patients with ER-negative breast cancer, suggesting it acts as a tumor suppressor by inhibiting the PI3K/AKT pathway.
Article Abstract
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.
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| http://dx.doi.org/10.1016/j.ccell.2015.07.003 | DOI Listing |
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