https://scholars.lib.ntu.edu.tw/handle/123456789/512354
標題: | EGFR-L858R mutant enhances lung adenocarcinoma cell invasive ability and promotes malignant pleural effusion formation through activation of the CXCL12-CXCR4 pathway | 作者: | Tsai M.-F. Chang T.-H. SHANG-GIN WU Yang H.-Y. Hsu Y.-C. PAN-CHYR YANG JIN-YUAN SHIH |
公開日期: | 2015 | 出版社: | Nature Publishing Group | 卷: | 5 | 起(迄)頁: | 13574 | 來源出版物: | Scientific Reports | 摘要: | Malignant pleural effusion (MPE) is a common clinical problem in non-small cell lung carcinoma (NSCLC) patients; however, the underlying mechanisms are still largely unknown. Recent studies indicate that the frequency of the L858R mutant form of the epidermal growth factor receptor (EGFR-L858R) is higher in lung adenocarcinoma with MPE than in surgically resected specimens, suggesting that lung adenocarcinoma cells harboring this mutation tend to invade the adjacent pleural cavity. The purpose of this study was to clarify the relationship between the EGFR-L858R mutation and cancer cell invasion ability and to investigate the molecular mechanisms involved in the formation of MPE. We found that expression of EGFR-L858R in lung cancer cells resulted in up-regulation of the CXCR4 in association with increased cancer cell invasive ability and MPE formation. Ectopic expression of EGFR-L858R in lung cancer cells acted through activation of ERK signaling pathways to induce the expression of CXCR4. We also indicated that Inhibition of CXCR4 with small interfering RNA, neutralizing antibody, or receptor antagonist significantly suppressed the EGFR-L858R-dependent cell invasion. These results suggest that targeting the production of CXCR4 and blocking the CXCL12-CXCR4 pathway might be effective strategies for treating NSCLCs harboring a specific type of EGFR mutation. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84941145860&doi=10.1038%2fsrep13574&partnerID=40&md5=419553894291f85a2acfccc77ca86cd1 https://scholars.lib.ntu.edu.tw/handle/123456789/512354 |
ISSN: | 2045-2322 | DOI: | 10.1038/srep13574 | SDG/關鍵字: | chemokine receptor CXCR4; CXCL12 protein, human; CXCR4 protein, human; EGFR protein, human; epidermal growth factor receptor; stromal cell derived factor 1; adenocarcinoma; genetics; human; lung tumor; malignant pleura effusion; metabolism; mutation; pathology; signal transduction; tumor cell line; tumor invasion; Adenocarcinoma; Cell Line, Tumor; Chemokine CXCL12; Humans; Lung Neoplasms; Mutation; Neoplasm Invasiveness; Pleural Effusion, Malignant; Receptor, Epidermal Growth Factor; Receptors, CXCR4; Signal Transduction |
顯示於: | 醫學系 |
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