https://scholars.lib.ntu.edu.tw/handle/123456789/586049
標題: | PINK1-Mediated Inhibition of EGFR Dimerization and Activation Impedes EGFR-Driven Lung Tumorigenesis | 作者: | Lin, Emily Pei-Ying Huang, Bo-Tsang Lai, Wei-Yun Tseng, Yi-Ting Yang, Shuenn-Chen Kuo, Hao-Cheng PAN-CHYR YANG |
公開日期: | 2021 | 卷: | 81 | 期: | 7 | 來源出版物: | Cancer research | 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. SIGNIFICANCE: This study identifies PINK1 as a critical tumor suppressor that impedes EGFR dimerization and highlights PINK1-CTD as a potential therapeutic agent in EGFR-driven lung cancer. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/586049 | ISSN: | 00085472 | DOI: | 10.1158/0008-5472.CAN-20-2582 | SDG/關鍵字: | epidermal growth factor receptor; protein serine threonine kinase; PTEN induced kinase 1; unclassified drug; EGFR protein, human; epidermal growth factor receptor; protein kinase; PTEN-induced putative kinase; animal cell; animal experiment; animal model; |
顯示於: | 醫學系 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。