The influences of mechanosignaling on cancer metabolic reprogramming and cell assembly
Prof. Chi-Shuo Chen (陳之碩)
Department of Biomedical and Environmental Sciences, NTHU
Physical microenvironment can regulate the cell fate from various perspectives. Here, we studied the influences of substrate stiffness on cell metabolism and cell assembly. First, we investigated the compounding influences of hypoxia and substrate stiffness, two critical physical features of tissue fibrosis, on the cancer metabolic shift. Our results suggested a counter influence of hypoxia and substrate stiffness on glucose consumption, but fructose bi-phosphate aldolase B can reverse this into synergistic effect on aerobic glycolysis. In the second part, we demonstrated how mechanical signals can drive the 3-dimensional cell assembly in vitro. The formation of tumor spheroid plays important roles in cancer progression, and the colonization of cancer cells enhance stem-like properties and elevate the capabilities of proliferation, anti- apoptosis, therapeutic resistance, metastasis and cancer recurrence. By measuring intercellular traction force, a tug-of-war model was established to interpret the imbalanced traction force in the 3-dimensional tumor spheroid formation. The quantitative mRNA results also indicated gap junctions are associated with tumor formation progress. In summary, our results highlight the essential roles of physical microenvironment in tumor progression, and extend our understanding about the complexity of mechanotransduction in cancer.