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

Lisa M Ooms1, Lauren C Binge1, Elizabeth M Davies1

  • 1Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.

Cancer Cell
|August 13, 2015
PubMed

Insights

The inositol polyphosphate 5-phosphatase PIPP (INPP5J) acts as a breast cancer tumor suppressor. Its depletion increases tumor growth but paradoxically reduces metastasis by inhibiting PI3K/AKT signaling.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Metastasis is a primary driver of breast cancer mortality.
  • Phosphoinositide 3-kinase (PI3K)/AKT signaling pathways are crucial for breast cancer cell proliferation and migration.
  • Inositol polyphosphate 5-phosphatases' role as tumor suppressors in breast cancer remains largely unexplored.

Purpose of the Study:

  • To investigate the role of the inositol polyphosphate 5-phosphatase PIPP (INPP5J) in breast cancer.
  • To determine PIPP's impact on PI3K/AKT signaling and its implications for tumor growth and metastasis.

Main Methods:

  • Depletion of PIPP (INPP5J) in breast cancer cells.
  • Assessment of cell transformation, migration, and invasion.
  • In vivo studies using oncogene-driven breast cancer models.
  • Analysis of PIPP mRNA expression in human breast cancer tissues.

Main Results:

  • PIPP depletion enhanced breast cancer cell transformation but reduced cell migration and invasion.
  • Pipp ablation accelerated tumor growth in vivo.
  • Paradoxically, Pipp ablation reduced metastasis, mediated by regulating AKT1-dependent tumor cell migration.
  • Reduced PIPP mRNA expression correlated with poorer outcomes in human ER-negative breast cancers.

Conclusions:

  • PIPP functions as a suppressor of oncogenic PI3K/AKT signaling in breast cancer.
  • PIPP plays a dual role in breast cancer, promoting metastasis suppression while potentially driving tumor growth.
  • Targeting PIPP may offer new therapeutic strategies for breast cancer, particularly ER-negative subtypes.

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