Induced sensitivity to EGFR inhibitors is mediated by palmitoylated cysteine 1025 of EGFR and requires oncogenic Kras.

ABSTRACT: Currently, there are no effective therapeutic strategies targeting Kras driven cancers, and therefore, identifying new targeted therapies and overcoming drug resistance have become paramount for effective long-term cancer therapy. We have found that reducing expression of the palmitoyl transferase DHHC20 increases cell death induced by the EGFR inhibitor gefitinib in Kras and EGFR mutant cell lines, but not MCF7 cells harboring wildtype Kras. We show that the increased gefitinib sensitivity in cancer cells induced by DHHC20 inhibition is mediated directly through loss of palmitoylation on a previously identified cysteine residue in the C-terminal tail of EGFR. We utilized an EGFR point mutant in which the palmitoylated cysteine 1025 is mutated to alanine (EGFR^C1025A), that resul

SUBMITTER: Kharbanda A 

PROVIDER: S-EPMC5636688 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature