SOX2 and osteosarcoma: In contrast, self-renewal capacity, differentiation potential, and drug resistance of osteosarcoma cells were unequivocally improved with reduced matrix stiffness and upregulated the expression of Sox2, Oct4 and Nanog, indicating that stiffening of the ECM has multiple functions in mediating tumor growth: the softer substrate is beneficial for maintaining the stem-like properties of osteosarcoma CSCs, while a more stiffer substrate than physiological state may contribute to tumor growth and metastasis [55].