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

<h2>Summary</h2> 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 <i>KRT18</i>, <i>HSPA6</i>, and <i>PKP3</i>, 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.