Dr. Yang, Pan-Chyr 's publons link picture

Dr. Yang, Pan-Chyr

Joint Appointment Research Fellow
Academician, Academia Sinica
  • 02-27899149 (Lab) (Room No: 511)
  • 02-27858594 (Fax)

Specialty:
  • Cell and Molecular Biology
  • Cancer genomics

Education and Positions:
  • M.D., Ph.D. National Taiwan University


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

Dr. Yang, Pan-Chyr
Cancer Research, Feb 09, 2021

 

EGFR is established as a driver of lung cancer, yet the regulatory machinery underlying its oncogenic activity is not fully understood. 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 (TKD). 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.