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Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors
08:45

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors

Published on: July 17, 2020

The role of Shp2 (PTPN11) in cancer

M Golam Mohi1, Benjamin G Neel

  • 1Department of Pharmacology, SUNY Upstate Medical University, WHA #3319, 750 East Adams Street, Syracuse, NY 13020, USA.

Current Opinion in Genetics & Development
|January 18, 2007
PubMed

Insights

Protein-tyrosine phosphatases (PTPs) play critical roles in cellular processes. While PTEN is a tumor suppressor, Shp2, another PTP, acts as an oncogene in leukemia and solid tumors, offering potential therapeutic targets.

Area of Science:

  • Cellular biology
  • Molecular oncology
  • Biochemistry

Background:

  • Tyrosyl phosphorylation, regulated by protein-tyrosine kinases (PTKs) and protein-tyrosine phosphatases (PTPs), is crucial for cellular functions.
  • While PTK alterations are linked to cancer, the roles of PTPs in normal cells and oncogenesis were less understood.
  • PTEN, a PTP superfamily member, is a known tumor suppressor gene.

Purpose of the Study:

  • To elucidate the role of PTPs, specifically Shp2, in cellular processes and cancer.
  • To investigate Shp2 as a potential oncogene and therapeutic target in various cancers.

Main Methods:

  • Review of existing literature on PTPs, PTKs, and their roles in cellular signaling and cancer.
  • Analysis of genetic alterations and activation mechanisms of Shp2 in different cancer types.

Main Results:

  • Shp2, a SH2 domain-containing phosphatase, is identified as a bona fide oncogene.
  • Mutations in Shp2 are observed in several leukemias.
  • Shp2 is hyperactivated through various mechanisms in some solid tumors.

Conclusions:

  • Shp2's oncogenic activity highlights the critical role of PTPs in cancer development.
  • Understanding Shp2 and other PTPs' contribution to oncogenesis can reveal new insights into disease pathogenesis.
  • Targeting Shp2 and related PTPs may offer novel strategies for anti-neoplastic drug development.

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