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Updated: Jul 4, 2025

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

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Re-expression of epigenetically silenced PTPRR by histone acetylation sensitizes RAS-mutant lung adenocarcinoma to

Tingting Du1,2,3, Xiaowen Hu4, Zhenyan Hou1

  • 1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.

Cellular and Molecular Life Sciences : CMLS
|January 27, 2024
PubMed

Insights

Silenced protein tyrosine phosphatase receptor type R (PTPRR) is linked to poor prognosis in RAS-mutant lung cancer. Targeting epigenetic silencing of PTPRR with HDAC and SHP2 inhibitors offers a promising new treatment strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Protein tyrosine phosphatase receptor type R (PTPRR) is involved in mitogen-activated protein kinase (MAPK) signaling in tumor development.
  • RAS gene mutations are common in lung adenocarcinoma, leading to MAPK pathway hyperactivation.
  • The regulatory mechanism of PTPRR in RAS-mutant lung adenocarcinoma remains unclear.

Purpose of the Study:

  • To investigate the role and regulation of PTPRR in RAS-mutant lung adenocarcinoma.
  • To explore potential therapeutic strategies targeting PTPRR.

Main Methods:

  • Analysis of patient data from The Cancer Genome Atlas and Gene Expression Omnibus.
  • In vitro and in vivo experiments involving PTPRR expression and inhibition of SHP2 and HDAC.
  • Chromatin immunoprecipitation assays to assess histone acetylation and PTPRR transcription.

Main Results:

  • Silenced PTPRR expression correlated positively with poor prognosis in lung adenocarcinoma.
  • Exogenous PTPRR expression inhibited lung cancer cell proliferation and migration.
  • Combined inhibition of HDAC and SHP2 synergistically suppressed tumor progression by restoring PTPRR transcription and controlling ERK1/2 phosphorylation.

Conclusions:

  • Epigenetic silencing of PTPRR is a mechanism in RAS-mutant lung cancer.
  • Combination therapy targeting HDAC and SHP2 presents a novel therapeutic strategy for RAS-mutant lung cancer.
Keywords:
Anti-cancer drugsDrug combinationEpigeneticsSignaling pathwayTargeted therapy

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