| First Author | Chen CL | Year | 2015 |
| Journal | Biochem Biophys Res Commun | Volume | 466 |
| Issue | 3 | Pages | 578-84 |
| PubMed ID | 26385178 | Mgi Jnum | J:232947 |
| Mgi Id | MGI:5780499 | Doi | 10.1016/j.bbrc.2015.09.085 |
| Citation | Chen CL, et al. (2015) Loss of PTEN causes SHP2 activation, making lung cancer cells unresponsive to IFN-gamma. Biochem Biophys Res Commun 466(3):578-84 |
| abstractText | Src homology-2 domain-containing phosphatase (SHP) 2, an oncogenic phosphatase, inhibits type II immune interferon (IFN)-gamma 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-gamma 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-gamma-induced IFN regulatory factor 1 activation and CD54 expression. Artificially silencing PTEN expression in A549 cells also caused cells to be unresponsive to IFN-gamma without affecting IFN-gamma receptor expression. IFN-gamma-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-gamma-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-gamma. |
