Enhanced YAP expression leads to EGFR TKI resistance in lung adenocarcinomas

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

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Article number271
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

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Epidermal Growth Factor Receptor
Protein-Tyrosine Kinases
Proteins
Drug Resistance
Adenocarcinoma of lung
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Neoplasms
Epithelial-Mesenchymal Transition
National Health Programs
Taiwan
Oncogenes
Heterografts
Nude Mice
Small Interfering RNA
Lung Neoplasms
Cell Proliferation
Databases
Recurrence
Mutation
Survival

ASJC Scopus subject areas

  • General

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Enhanced YAP expression leads to EGFR TKI resistance in lung adenocarcinomas. / Lee, Ting Fang; Tseng, Yu Chi; Nguyen, Phung Anh; Li, Yu Chuan; Ho, Chao Chi; Wu, Cheng Wen.

In: Scientific Reports, Vol. 8, No. 1, 271, 01.12.2018.

Research output: Contribution to journalArticle

Lee, Ting Fang ; Tseng, Yu Chi ; Nguyen, Phung Anh ; Li, Yu Chuan ; Ho, Chao Chi ; Wu, Cheng Wen. / Enhanced YAP expression leads to EGFR TKI resistance in lung adenocarcinomas. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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