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Please use this identifier to cite or link to this item:
http://ir.nhri.org.tw/handle/3990099045/6288
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| Title: | EGFR and myosin II inhibitors cooperate to suppress EGFR-T790M-mutant NSCLC cells |
| Authors: | Chiu, HC;Chang, TY;Huang, CT;Chao, YS;Hsu, JT |
| Contributors: | Institute of Biotechnology and Pharmaceutical Research |
| Abstract: | An acquired mutation (T790M) in the epidermal growth factor receptor (EGFR) accounts for half of all relapses in non-small cell lung cancer (NSCLC) patients who initially respond to EGFR kinase inhibitors. In this study, we demonstrated for the first time that EGFR-T790M interacts with the cytoskeletal components, myosin heavy chain 9 (MYH9) and beta-actin, in the nucleus of H1975 cells carrying the T790M-mutant EGFR. The interactions of EGFR with MYH9 and beta-actin were reduced in the presence of blebbistatin, a specific inhibitor for the MYH9-beta-actin interaction, suggesting that the EGFR interaction with MYH9 and beta-actin is affected by the integrity of the cytoskeleton. These physical interactions among MYH9, beta-actin, and EGFR were also impaired by CL-387,785, a kinase inhibitor for EGFR-T790M. Furthermore, CL-387,785 and blebbistatin interacted in a synergistic fashion to suppress cell proliferation and induce apoptosis in H1975 cells. The combination of CL-387,785 and blebbistatin enhanced the down-regulation of cyclooxygenase-2 (COX-2), a transcriptional target of nuclear EGFR. Overall, our findings demonstrate that disrupting EGFR interactions with the cytoskeletal components enhanced the anti-cancer effects of CL-387,785 against H1975 cells, suggesting a novel therapeutic approach for NSCLC cells that express the drug-resistant EGFR-T790M. |
| Date: | 2012-06 |
| Relation: | Molecular Oncology. 2012 Jun;6(3):299-310. |
| Link to: | http://dx.doi.org/10.1016/j.molonc.2012.02.001 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1574-7891&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000305374900004 |
| Cited Times(Scopus): | http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84862780685 |
| Appears in Collections: | [徐祖安] 期刊論文
[趙宇生(2002-2013)] 期刊論文
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| PUB22366308.pdf | | 1573Kb | Adobe PDF | 432 | View/Open |
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