HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Loss of PTEN causes SHP2 activation, making lung cancer cells unresponsive to IFN-γ.

Abstract
Src homology-2 domain-containing phosphatase (SHP) 2, an oncogenic phosphatase, inhibits type II immune interferon (IFN)-γ signaling by subverting signal transducers and activators of transcription 1 tyrosine phosphorylation and activation. For cancer immunoediting, this study aimed to investigate the decrease of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a tumor suppressor protein, leading to cellular impairment of IFN-γ signaling. In comparison with human lung adenocarcinoma A549 cells, the natural PTEN loss in another human lung adenocarcinoma line, PC14PE6/AS2 cells, presents reduced responsiveness in IFN-γ-induced IFN regulatory factor 1 activation and CD54 expression. Artificially silencing PTEN expression in A549 cells also caused cells to be unresponsive to IFN-γ without affecting IFN-γ receptor expression. IFN-γ-induced inhibition of cell proliferation and cytotoxicity were demonstrated in A549 cells but were defective in PC14PE6/AS2 cells and in PTEN-deficient A549 cells. Aberrant activation of SHP2 by ROS was specifically shown in PC14PE6/AS2 cells and PTEN-deficient A549 cells. Inhibiting ROS and SHP2 rescued cellular responses to IFN-γ-induced cytotoxicity and inhibition of cell proliferation in PC14PE6/AS2 cells. These results demonstrate that a decrease in PTEN facilitates ROS/SHP2 signaling, causing lung cancer cells to become unresponsive to IFN-γ.
AuthorsChia-Ling Chen, Tzu-Hui Chiang, Po-Chun Tseng, Yu-Chih Wang, Chiou-Feng Lin
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 466 Issue 3 Pg. 578-84 (Oct 23 2015) ISSN: 1090-2104 [Electronic] United States
PMID26385178 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier Inc. All rights reserved.
Chemical References
  • Reactive Oxygen Species
  • Interferon-gamma
  • PTPN11 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • PTEN Phosphohydrolase
  • PTEN protein, human
Topics
  • Adenocarcinoma (immunology, metabolism, pathology)
  • Adenocarcinoma of Lung
  • Cell Line, Tumor
  • Cell Proliferation
  • Enzyme Activation
  • Gene Knockdown Techniques
  • Humans
  • Interferon-gamma (immunology, metabolism)
  • Lung Neoplasms (immunology, metabolism, pathology)
  • PTEN Phosphohydrolase (antagonists & inhibitors, deficiency, genetics)
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 (metabolism)
  • RNA Interference
  • Reactive Oxygen Species (metabolism)
  • Signal Transduction
  • Tumor Escape

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: