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Updated: Jun 21, 2026

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry
08:07

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

Published on: July 26, 2019

Evidence that inositol polyphosphate 4-phosphatase type II is a tumor suppressor that inhibits PI3K signaling

Christina Gewinner1, Zhigang C Wang, Andrea Richardson

  • 1Division of Signal Transduction, Beth Israel Deaconess Medical Center, Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.

Cancer Cell
|August 4, 2009
PubMed

Insights

Inositol polyphosphate 4-phosphatase type II (INPP4B) acts as a tumor suppressor by regulating Akt activation and cell growth. Loss of INPP4B is linked to aggressive breast and ovarian cancers, impacting patient survival.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • Inositol polyphosphate 4-phosphatase type II (INPP4B) is implicated in cell signaling pathways.
  • The role of INPP4B in cancer, particularly its relationship with Akt activation and tumor suppression, requires further elucidation.

Purpose of the Study:

  • To investigate the function of INPP4B in human epithelial cells and its impact on Akt signaling.
  • To determine the role of INPP4B in tumor growth and its potential as a tumor suppressor.
  • To examine the correlation between INPP4B expression, cancer development, and patient survival.

Main Methods:

  • Knockdown and overexpression of INPP4B in human epithelial cells.
  • Analysis of Akt activation, anchorage-independent growth, and cell motility.
  • Xenograft experiments to assess tumor growth.
  • Analysis of phosphatidylinositol phosphate hydrolysis.
  • Loss of heterozygosity (LOH) analysis in breast and ovarian cancer samples.

Main Results:

  • Knockdown of INPP4B enhanced Akt activation, anchorage-independent growth, and cell motility, similar to PTEN knockdown.
  • Overexpression of INPP4B reduced tumor growth in xenograft models.
  • INPP4B preferentially hydrolyzes phosphatidylinositol-3,4-bisphosphate (PI(3,4)P(2)), suggesting a cooperative role with phosphatidylinositol-3.4.5-triphosphate (PI(3,4,5)P(3)) in Akt activation.
  • Dual knockdown of INPP4B and PTEN induced cellular senescence.
  • Loss of heterozygosity at the INPP4B locus was observed in basal-like breast and ovarian cancers, correlating with reduced patient survival.

Conclusions:

  • INPP4B functions as a tumor suppressor by negatively regulating Akt activation and promoting cell transformation.
  • The PI(3,4)P(2) hydrolysis activity of INPP4B is critical for its tumor-suppressive function.
  • Loss of INPP4B is a significant event in the development of certain breast and ovarian cancers and is associated with poor prognosis.

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