EIF4E S209 phosphorylation licenses myc- and stress-driven oncogenesis.

ABSTRACT: To better understand a role of eIF4E S209 in oncogenic translation, we generated EIF4E^S209A/+ heterozygous knockin (4EKI) HCT 116 human colorectal cancer (CRC) cells. 4EKI had little impact on total eIF4E levels, cap binding or global translation, but markedly reduced HCT 116 cell growth in spheroids and mice, and CRC organoid growth. 4EKI strongly inhibited Myc and ATF4 translation, the integrated stress response (ISR)-dependent glutamine metabolic signature, AKT activation and proliferation in vivo. 4EKI inhibited polyposis in Apc^Min/+ mice by suppressing Myc protein and AKT activation. Furthermore, p-eIF4E was highly elevated in CRC precursor lesions in mouse and human. p-eIF4E cooperated with mutant KRAS to promote Myc and ISR-dependent glutam

SUBMITTER: Ruan H 

PROVIDER: S-EPMC7665890 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature