Enhanced YAP expression leads to EGFR TKI resistance in lung adenocarcinomas
| Autor: | Yu Chi Tseng, Cheng-Wen Wu, Ting Fang Lee, Yu-Chuan Li, Phung Anh Nguyen, Chao-Chi Ho |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Lung Neoplasms medicine.medical_treatment Cell lcsh:Medicine Cell Cycle Proteins Targeted therapy Small hairpin RNA Mice 0302 clinical medicine Epidermal growth factor receptor lcsh:Science Multidisciplinary biology Nuclear Proteins Prognosis ErbB Receptors Gene Expression Regulation Neoplastic medicine.anatomical_structure 030220 oncology & carcinogenesis Adenocarcinoma Cell Survival Adenocarcinoma of Lung Antineoplastic Agents Article 03 medical and health sciences Downregulation and upregulation Cell Line Tumor medicine Animals Humans Lung cancer Protein Kinase Inhibitors Cell Proliferation Cell growth business.industry lcsh:R medicine.disease Xenograft Model Antitumor Assays respiratory tract diseases Disease Models Animal 030104 developmental biology Drug Resistance Neoplasm Cancer research biology.protein lcsh:Q business Transcription Factors |
| Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-8 (2018) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-017-18527-z |
| Popis: | Epidermal growth factor receptor (EGFR) mutation is prevalently expressed in lung adenocarcinoma cases and acts as one of the major driving oncogenes. EGFR tyrosine kinase inhibitors (TKIs) have been used in patients with EGFR-mutant as an effective targeted therapy in lung adenocarcinoma, but drug resistance and tumor recurrence inevitably occurs. Recently, Yes-associate protein (YAP) has been reported to promote multiple cancer cell properties, such as promoting cell proliferation, epithelial-mesenchymal transition and drug resistance. This study investigated the roles of YAP in TKI-resistant lung adenocarcinoma. In TKI-sensitive cells, enhanced YAP expression leads to TKI resistant. Also, upregulated YAP expression and activation were detected in long-term TKI-induced resistant cells. With reduced YAP expression using shRNA or YAP inhibitors, TKI-resistant cells become TKI-sensitive. reduced xenograft tumor size in nude mice and Moreover, combined EGFR TKI and a YAP inhibitor, statin, prolonged survival among lung cancer patients analyzed by Taiwan National Health Insurance Research database. These observations revealed the importance of YAP in promoting TKI-resistance and combined YAP inhibition can be a potential therapy delaying the occurrence of TKI-resistance in lung adenocarcinoma. |
| Databáze: | OpenAIRE |
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