Single-cell and spatial transcriptomics reveal that THBS1 induces radiation resistance in TNBC through the interaction between myCAF and TOPBP1⁺ tumor cells

Radiation resistance remains a clinical challenge in the treatment of triple-negative breast cancer (TNBC) and its mechanisms are not yet fully understood. We integrated single-cell RNA sequencing, spatial transcriptomics, and prognostic data to perform analyses such as intercellular communication, pseudo-temporal trajectories, and GSEA and validated the results using experiments including qPCR, single-cell sequencing and flow cytometry. This study identified a unique subpopulation of epithelial cells, designated TOPBP1⁺ E.T. cells, which retain normal epithelial transcriptional profiles and are associated with poor patient prognosis. myCAF communicates with this cell cluster via the THBS1 signaling pathway, activating the NOTCH signaling pathway to promote resistance to radiotherapy. THBS1 plays a pivotal role in mediating radioresistance in triple-negative breast cancer, positioning it as a promising therapeutic target.