FOXA1 O-GlcNAcylation-mediated transcriptional switch governs metastasis capacity in breast cancer.

ABSTRACT: FOXA1, a transcription factor involved in epigenetic reprogramming, is crucial for breast cancer progression. However, the mechanisms by which FOXA1 achieves its oncogenic functions remain elusive. Here, we demonstrate that the O-linked β-N-acetylglucosamine modification (O-GlcNAcylation) of FOXA1 promotes breast cancer metastasis by orchestrating the transcription of numerous metastasis regulators. O-GlcNAcylation at Thr⁴³², Ser⁴⁴¹, and Ser⁴⁴³ regulates the stability of FOXA1 and promotes its assembly with chromatin. O-GlcNAcylation shapes the FOXA1 interactome, especially triggering the recruitment of the transcriptional repressor methyl-CpG binding protein 2 and consequently stimulating FOXA1 chromatin-binding sites to switch to chromatin loci of

SUBMITTER: Liu Y 

PROVIDER: S-EPMC10438466 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature