RB/E2F1 as a Master Regulator of Cancer Cell Metabolism in Advanced Disease.

ABSTRACT: Loss of the retinoblastoma (RB) tumor suppressor protein is a critical step in reprogramming biological networks that drive cancer progression, although mechanistic insight has been largely limited to the impact of RB loss on cell-cycle regulation. Here, isogenic modeling of RB loss identified disease stage-specific rewiring of E2F1 function, providing the first-in-field mapping of the E2F1 cistrome and transcriptome after RB loss across disease progression. Biochemical and functional assessment using both in vitro and in vivo models identified an unexpected, prominent role for E2F1 in regulation of redox metabolism after RB loss, driving an increase in the synthesis of the antioxidant glutathione, specific to advanced disease. These E2F1-dependent events resulted in protecti

SUBMITTER: Mandigo AC 

PROVIDER: S-EPMC8419081 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature