Enhanced YAP expression leads to EGFR TKI resistance in lung adenocarcinomas View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-01-10

AUTHORS

Ting-Fang Lee, Yu-Chi Tseng, Phung Anh Nguyen, Yu-Chuan Li, Chao-Chi Ho, Cheng-Wen Wu

ABSTRACT

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. More... »

PAGES

271

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-017-18527-z

DOI

http://dx.doi.org/10.1038/s41598-017-18527-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1100203126

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29321482


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