Glioblastoma mutations alter EGFR dimer structure to prevent ligand bias.

ABSTRACT: The epidermal growth factor receptor (EGFR) is frequently mutated in human cancer^1,2, and is an important therapeutic target. EGFR inhibitors have been successful in lung cancer, where mutations in the intracellular tyrosine kinase domain activate the receptor¹, but not in glioblastoma multiforme (GBM)³, where mutations occur exclusively in the extracellular region. Here we show that common extracellular GBM mutations prevent EGFR from discriminating between its activating ligands⁴. Different growth factor ligands stabilize distinct EGFR dimer structures⁵ that signal with different kinetics to specify or bias outcome^5,6. EGF itself induces strong symmetric dimers that signal transiently to promote proliferation. Epiregulin (

SUBMITTER: Hu C 

PROVIDER: S-EPMC8857055 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature