ECM Stiffness and Breast Cancer Dormancy
This study investigates the role of extracellular matrix (ECM) stiffness in regulating dormancy and reactivation of disseminated tumor cells (DTCs) in breast cancer, using the human DTC-derived BC-M1 cell line. BC-M1 cells were cultured on ECM substrates with soft (4 kPa) and stiff (25 kPa) mechanical properties, mimicking healthy and fibrotic tissues, respectively. Single-cell RNA sequencing (scRNA-seq) was performed to profile gene expression and identify subpopulations, revealing 305 differentially expressed genes between conditions. Soft substrates promoted dormancy-associated and mesenchymal gene programs, while stiff matrices induced epithelial traits and suppressed dormancy markers. Gene set enrichment analysis (GSEA), trajectory inference, and gene regulatory network (GRN) analysis identified molecular pathways linking stiffness to dormancy escape.  These findings highlight ECM stiffness as a critical regulator of breast cancer dormancy, offering insights into preventing metastatic recurrence.