Hypoxic stress incites HIF1α-driven ribosome biogenesis that can be exploited by targeting RNA Polymerase I.

ABSTRACT: Intratumoral low oxygen tension promotes cancer cell invasion and metastasis. Hypoxia-Inducible Factor 1-alpha (HIF1α) is the principal transcription factor orchestrating cellular responses to hypoxic stress, mediating the regulation of genes implicated in adapting to perturbations in oxygen homeostasis. Here, we describe our findings that functionally demonstrate a nucleolar localization domain in HIF1ɑ that enables HIF1ɑ to translocate to the nucleolus. Nucleolar HIF1ɑ binds the ribosomal DNA promoter and upregulates RNA Polymerase I activity leading to dysregulated ribosomal RNA transcription and consequently enhanced ribosome biogenesis. Ribosome biogenesis is important in supporting cellular metabolic processes and invasion and metastasis. Our findings are recapitulated in breast tumo

SUBMITTER: Elhamamsy A 

PROVIDER: S-EPMC12391393 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature