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Title: 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. - Highlights: • This study demonstrates that PTEN decrease causesmore » cellular unresponsive to IFN-γ. • Lung cancer cells with PTEN deficiency show unresponsive to IFN-γ signaling. • PTEN decrease inhibits IFN-γ-induced CD54, cell proliferation inhibition, and cytotoxicity. • ROS-mediated SHP2 activation makes PTEN-deficient cells unresponsive to IFN-γ.« less

Authors:
 [1]; ;  [2];  [3];  [3];  [4]
  1. Translational Research Center, Taipei Medical University, Taipei 110, Taiwan (China)
  2. Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan (China)
  3. Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan (China)
  4. (China)
Publication Date:
OSTI Identifier:
22592775
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 466; Journal Issue: 3; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CARCINOMAS; CELL PROLIFERATION; CHROMOSOMES; INHIBITION; INTERFERON; LUNGS; PHOSPHORYLATION; RECEPTORS; TOXICITY; TRANSCRIPTION; TYROSINE

Citation Formats

Chen, Chia-Ling, Chiang, Tzu-Hui, Tseng, Po-Chun, Wang, Yu-Chih, Lin, Chiou-Feng, E-mail: cflin2014@tmu.edu.tw, and Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. Loss of PTEN causes SHP2 activation, making lung cancer cells unresponsive to IFN-γ. United States: N. p., 2015. Web. doi:10.1016/J.BBRC.2015.09.085.
Chen, Chia-Ling, Chiang, Tzu-Hui, Tseng, Po-Chun, Wang, Yu-Chih, Lin, Chiou-Feng, E-mail: cflin2014@tmu.edu.tw, & Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. Loss of PTEN causes SHP2 activation, making lung cancer cells unresponsive to IFN-γ. United States. doi:10.1016/J.BBRC.2015.09.085.
Chen, Chia-Ling, Chiang, Tzu-Hui, Tseng, Po-Chun, Wang, Yu-Chih, Lin, Chiou-Feng, E-mail: cflin2014@tmu.edu.tw, and Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. Fri . "Loss of PTEN causes SHP2 activation, making lung cancer cells unresponsive to IFN-γ". United States. doi:10.1016/J.BBRC.2015.09.085.
@article{osti_22592775,
title = {Loss of PTEN causes SHP2 activation, making lung cancer cells unresponsive to IFN-γ},
author = {Chen, Chia-Ling and Chiang, Tzu-Hui and Tseng, Po-Chun and Wang, Yu-Chih and Lin, Chiou-Feng, E-mail: cflin2014@tmu.edu.tw and Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan},
abstractNote = {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. - Highlights: • This study demonstrates that PTEN decrease causes cellular unresponsive to IFN-γ. • Lung cancer cells with PTEN deficiency show unresponsive to IFN-γ signaling. • PTEN decrease inhibits IFN-γ-induced CD54, cell proliferation inhibition, and cytotoxicity. • ROS-mediated SHP2 activation makes PTEN-deficient cells unresponsive to IFN-γ.},
doi = {10.1016/J.BBRC.2015.09.085},
journal = {Biochemical and Biophysical Research Communications},
number = 3,
volume = 466,
place = {United States},
year = {Fri Oct 23 00:00:00 EDT 2015},
month = {Fri Oct 23 00:00:00 EDT 2015}
}