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Cancer Cell. 2015 Aug 10;28(2):155-69. doi: 10.1016/j.ccell.2015.07.003.

The Inositol Polyphosphate 5-Phosphatase PIPP Regulates AKT1-Dependent Breast Cancer Growth and Metastasis.

Author information

1
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
2
Garvan Institute of Medical Research, The Kinghorn Cancer Centre, Faculty of Medicine, St Vincent's Clinical School, University of NSW, Darlinghurst, NSW 2010, Australia.
3
Ozgene Pty Ltd, Bentley DC, WA 6983, Australia.
4
Department of Anatomical Pathology, Alfred Hospital, Prahran, VIC 3181, Australia.
5
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia. Electronic address: christina.mitchell@monash.edu.

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.

PMID:
26267533
DOI:
10.1016/j.ccell.2015.07.003
[Indexed for MEDLINE]
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