Oncogenic RTKs sensitize cancer cells to ferroptosis via c-Myc mediated upregulation of ACSL4.

ABSTRACT: Alteration or abnormal activation of RTKs have been recurrently observed and recognized as an important driving factor in the progression of many human cancers. Ferroptosis, an iron-dependent form of regulated necrosis triggered by the accumulation of lethal lipid peroxides on cell membranes, has been implicated in various tumor types. Here we reported that oncogenic RTKs/RAS/RAF/c-Myc axis promotes cancer cells to ferroptosis. Mechanistically, c-Myc binds to the promoter region of ACSL4 and promotes the expression of ACSL4, thereby sensitizes cells to ferroptosis. We further showed that RTKs/RAS/RAF promote ferroptosis by upregulating c-Myc mediated expression of ACSL4 in cancer cells. Notably, overexpression of RTKs enhances the vulnerability of melanoma to the ferroptosis inducer in mou

SUBMITTER: Sun N 

PROVIDER: S-EPMC11603294 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature