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.
|
Authors | Chia-Ling Chen, Tzu-Hui Chiang, Po-Chun Tseng, Yu-Chih Wang, Chiou-Feng Lin |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 466
Issue 3
Pg. 578-84
(Oct 23 2015)
ISSN: 1090-2104 [Electronic] United States |
PMID | 26385178
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright © 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
|