Nuclear to cytoplasmic transport is a druggable dependency in MYC-driven hepatocellular carcinoma.

ABSTRACT: The MYC oncogene is often dysregulated in human cancer, including hepatocellular carcinoma (HCC). MYC is considered undruggable to date. Here, we comprehensively identify genes essential for survival of MYC^high but not MYC^low cells by a CRISPR/Cas9 genome-wide screen in a MYC-conditional HCC model. Our screen uncovers novel MYC synthetic lethal (MYC-SL) interactions and identifies most MYC-SL genes described previously. In particular, the screen reveals nucleocytoplasmic transport to be a MYC-SL interaction. We show that the majority of MYC-SL nucleocytoplasmic transport genes are upregulated in MYC^high murine HCC and are associated with poor survival in HCC patients. Inhibiting Exportin-1 (XPO1) in vivo induces marked tumor regression in an autochthonous M

SUBMITTER: Deutzmann A 

PROVIDER: S-EPMC10834515 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature