Single-cell transcriptomics profiling elucidates RBP-driven metastatic signaling pathways in ER+ breast cancer

Summary Estrogen receptor-positive breast cancer progression involves extensive cellular remodeling, yet the contribution of RNA-binding proteins to this process remains incompletely defined. Here, we constructed a single-cell transcriptomic atlas of 198,286 cells from 39 samples spanning normal tissue, primary tumors, and metastatic lesions. We identified stage-specific transcriptional and post-transcriptional reprogramming across different cell types. Several RBPs, including KRT18, HSPA6, and PKP3, were progressively upregulated during malignant progression and associated with cytoskeletal remodeling, extracellular matrix interactions, and stress adaptation. Cell-cell communication analyses revealed metastasis-associated signaling programs involving TIMP1-MMP1 and TGFB1-COL7A1/MMP1, which were spatially enriched at tumor margins and invasive fronts. Functional perturbation experiments in ER⁺ breast cancer cells showed that TGF-β stimulation enhanced invasive behavior, whereas knockdown of MMP1 or COL7A1 attenuated epithelial-mesenchymal transition (EMT) marker expression and invasion. Together, our study delineates RBP-associated regulatory programs linking cellular state transitions to invasive signaling in ER⁺ breast cancer.