The inositol polyphosphate 5-Phosphatase PIPP regulates AKT1-Dependent breast cancer growth and metastasis

Lisa M Ooms, Lauren C Binge, Elizabeth M Davies, Parvin Rahman, James R W Conway, Rajendra Gurung, Daniel T Ferguson, Antonella Papa, Clare G Fedele, Jessica L Vieusseux, Ryan C C Chai, Frank Koentgen, John T Price, Tony Tiganis, Paul Timpson, Catriona A McLean, Christina Anne Mitchell

Research output: Contribution to journalArticleResearchpeer-review

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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.
Original languageEnglish
Pages (from-to)155-169
Number of pages15
JournalCancer Cell
Volume28
Issue number2
DOIs
Publication statusPublished - 10 Aug 2015

Cite this

Ooms, Lisa M ; Binge, Lauren C ; Davies, Elizabeth M ; Rahman, Parvin ; Conway, James R W ; Gurung, Rajendra ; Ferguson, Daniel T ; Papa, Antonella ; Fedele, Clare G ; Vieusseux, Jessica L ; Chai, Ryan C C ; Koentgen, Frank ; Price, John T ; Tiganis, Tony ; Timpson, Paul ; McLean, Catriona A ; Mitchell, Christina Anne. / The inositol polyphosphate 5-Phosphatase PIPP regulates AKT1-Dependent breast cancer growth and metastasis. In: Cancer Cell. 2015 ; Vol. 28, No. 2. pp. 155-169.
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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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The inositol polyphosphate 5-Phosphatase PIPP regulates AKT1-Dependent breast cancer growth and metastasis. / Ooms, Lisa M; Binge, Lauren C; Davies, Elizabeth M; Rahman, Parvin; Conway, James R W; Gurung, Rajendra; Ferguson, Daniel T; Papa, Antonella; Fedele, Clare G; Vieusseux, Jessica L; Chai, Ryan C C; Koentgen, Frank; Price, John T; Tiganis, Tony; Timpson, Paul; McLean, Catriona A; Mitchell, Christina Anne.

In: Cancer Cell, Vol. 28, No. 2, 10.08.2015, p. 155-169.

Research output: Contribution to journalArticleResearchpeer-review

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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

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