Oncogenic activation of SMYD3-SHCBP1 promotes breast cancer development and is coupled with resistance to immune therapy.

ABSTRACT: Breast cancer initiation and progression are driven by various oncogenic factors and their effects on the surrounding microenvironments. Through integrative analysis of ChIP-sequencing and RNA-sequencing with fast proliferating mammary epithelial cells from pregnant Brca1^MKO and wild type (WT) mice, we found that elevated Smyd3-Shcbp1 signaling is featured with activation of the Ras-MAPK pathway and increased transcription activity in both premalignant mammary epithelium and tumor cells. Smyd3-Shcbp1 signaling shapes the tumor immunosuppressive microenvironment (TIME) and is associated with immune therapy resistance to PD1 antibody treatment. Trametinib, a potent inhibitor of MEK/MAPK, could reverse the expression of Smyd3 and Shcbp1 in both Brca1 mutant and WT tumor bearing mic

SUBMITTER: Mo L 

PROVIDER: S-EPMC11954966 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature