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Updated: Apr 14, 2026

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry
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Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

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INPP4B Is a PtdIns(3,4,5)P3 Phosphatase That Can Act as a Tumor Suppressor

Satoshi Kofuji1, Hirotaka Kimura1, Hiroki Nakanishi2

  • 1Research Center for Biosignal, Akita University, Akita, Japan. Department of Medical Biology, Akita University Graduate School of Medicine, Akita, Japan.

Cancer Discovery
|April 18, 2015
PubMed
Abstract

Insights

Inositol polyphosphate 4-phosphatase B (INPP4B) restrains tumor growth by dephosphorylating PtdIns(3,4,5)P3, especially when PTEN is deficient. This discovery highlights INPP4B as a potential therapeutic target for specific cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Inositol polyphosphate 4-phosphatase B (INPP4B) is a known tumor suppressor in breast, ovarian, and prostate cancers.
  • The precise molecular mechanism of INPP4B's tumor-suppressive function remains largely unelucidated.
  • Mutations in INPP4B are observed in various human malignancies.

Purpose of the Study:

  • To investigate the molecular mechanism underlying INPP4B's tumor-suppressive role.
  • To determine if INPP4B acts as a phosphatase for phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3).
  • To explore the functional significance of INPP4B in the context of PTEN deficiency.

Main Methods:

  • In vitro biochemical assays to assess INPP4B's phosphatase activity.
  • In vivo studies using genetically modified mice with targeted Inpp4b and Pten mutations (Inpp4b(Δ/Δ) and Pten(+/-)).
  • Analysis of thyroid tissue for tumor development, metastasis, and molecular signaling pathways (AKT activation).

Main Results:

  • INPP4B directly dephosphorylates PtdIns(3,4,5)P3 in vitro.
  • Combined inactivation of Inpp4b and heterozygous Pten deletion in mice induced malignant thyroid cancers with lung metastases.
  • Simultaneous deletion of Inpp4b and Pten synergistically elevated PtdIns(3,4,5)P3 levels and activated AKT signaling in thyroid cells.

Conclusions:

  • INPP4B functions as a tumor suppressor, particularly crucial in PTEN-deficient conditions.
  • The PtdIns(3,4,5)P3 phosphatase activity of INPP4B acts as a compensatory mechanism against PI3K/AKT pathway hyperactivation.
  • INPP4B represents a potential therapeutic target for PTEN-deficient or PIK3CA-activated cancers.

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