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PTEN and Other PtdIns(3,4,5)P3 Lipid Phosphatases in Breast Cancer

Mariah P Csolle1, Lisa M Ooms1, Antonella Papa1

  • 1Cancer Program, Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.

International Journal of Molecular Sciences
|December 5, 2020
PubMed

Insights

PTEN, PIPP, SHIP2, and SYNJ2 phosphatases have distinct roles in breast cancer. While PTEN is a tumor suppressor, PIPP, SHIP2, and SYNJ2 show varied effects, impacting tumor growth, migration, and survival.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • The phosphoinositide 3-kinase (PI3K)/AKT pathway is crucial for cell growth and survival, and its hyperactivation is common in breast cancer.
  • PTEN acts as a tumor suppressor by negatively regulating the PI3K/AKT pathway.
  • Inositol polyphosphate 5-phosphatases (5-phosphatases) also modulate this pathway, with diverse roles in tumorigenesis.

Purpose of the Study:

  • To review the distinct regulatory functions of PTEN, PIPP, SHIP2, and SYNJ2 in breast cancer progression.
  • To elucidate the mechanisms by which dysregulation of these phosphoinositide phosphatases impacts mammary tumorigenesis.

Main Methods:

  • Literature review of studies on PTEN, PIPP, SHIP2, and SYNJ2 in breast cancer.
  • Analysis of the roles of these phosphatases in regulating the PI3K/AKT pathway and downstream cellular processes.
  • Examination of their impact on tumor growth, migration, and patient survival.

Main Results:

  • Reduced PIPP expression is linked to triple-negative breast cancer and poorer survival, paradoxically inhibiting migration despite promoting AKT phosphorylation.
  • Increased SHIP2 and SYNJ2 correlate with invasive disease and reduced survival, promoting tumorigenesis through AKT-dependent and independent pathways.
  • PTEN is a well-established tumor suppressor, frequently mutated in breast cancer.

Conclusions:

  • PTEN, PIPP, SHIP2, and SYNJ2 exhibit distinct functions and regulatory mechanisms in breast cancer.
  • The differential dysregulation of these phosphoinositide phosphatases significantly impacts breast cancer progression and patient outcomes.
  • Targeting these phosphatases may offer novel therapeutic strategies for breast cancer treatment.
Keywords:
AKTSrc homology 2-containing inositol phosphatase 2 (SHIP2)breast cancerinositol polyphosphate phosphatasesphosphatase tensin homolog deleted on chromosome 10 (PTEN)phosphoinositide 3-kinase (PI3K)proline rich inositol polyphosphate 5-phosphatase (PIPP)synaptojanin 2 (SYNJ2)

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