PINK1-mediated inhibition of EGFR dimerization and activation impedes EGFR-driven lung tumorigenesis

Pei-Ying Lin Emily Pei-Ying Lin, Bo Tsang Huang, Wei Yun Lai, Yi Ting Tseng, Shuenn Chen Yang, Hao Cheng Kuo, Pan Chyr Yang

研究成果: 雜誌貢獻文章同行評審

摘要

EGFR is established as a driver of lung cancer, yet the regulatory machinery underlying its oncogenic activity is not fully understood. PTEN-induced kinase 1 (PINK1) kinase is a key player in mitochondrial quality control, although its role in lung cancer and EGFR regulation is unclear. In this study, we show that PINK1 physically directly interacts with EGFR via the PINK1 C-terminal domain (PINK1-CTD) and the EGFR tyrosine kinase domain. This interaction constituted an endogenous steric hindrance to receptor dimerization and inhibited EGFR-mediated lung carcinogenesis. Depletion of PINK1 from lung cancer cells promoted EGFR dimerization, receptor activation, EGFR downstream signaling, and tumor growth. In contrast, overexpression of PINK1 or PINK1- CTD suppressed EGFR dimerization, activation, downstream signaling, and tumor growth. These findings identify key elements in the EGFR regulatory cascade and illustrate a new direction for the development of anti-EGFR therapeutics, suggesting translational potential of the PINK1-CTD in lung cancer.

原文英語
頁(從 - 到)1745-1757
頁數13
期刊Cancer Research
81
發行號7
DOIs
出版狀態已發佈 - 四月 2021

ASJC Scopus subject areas

  • 腫瘤科
  • 癌症研究

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