Stabilization of RUNX1 Induced by O-GlcNAcylation Promotes PDGF-BB-Mediated Resistance to CDK4/6 Inhibitors in Breast Cancer.

ABSTRACT: Cyclin-dependent kinases 4 and 6 (CDK4/6) are crucial in regulating cell-cycle progression and cancer development. Targeting CDK4/6 has shown considerable promise in treating various cancers, including breast cancer. Despite significant therapeutic efficacy, resistance to CDK4/6 inhibitors (CDK4/6i), such as palbociclib, remains a substantial hurdle in clinical practice. Using a coculture system, cytokine array, and quantitative high-throughput combinatorial screening, we discovered a mechanism by which the Runt-related transcription factor (RUNX) 1-platelet-derived growth factor (PDGF)-BB axis regulates palbociclib resistance in breast cancer cells. Specifically, RUNX1 functioned as a transcription factor to drive expression of PDGFB, leading to resistance to palbociclib by enhancing the

SUBMITTER: Zhou S 

PROVIDER: S-EPMC12625700 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature