ECM stiffness critically modulates breastcancer biology, driving cell proliferation, stemness, metastasis,and invasion through key signaling pathwayssuch as YAP/TAZ, Wnt/β-catenin,FAK, TWIST1, PI3K/AKT/mTORC1, and ROCK. Consequently, alterations in matrix stiffnesscan profoundly influence these signaling cascades, thereby affectingthe behavior of breast cancer cells, the functions of stromal cells,and responses to therapeutic interventions. The gene discussed is TWIST1; the disease is breast cancer.