Fig. 6.

A schematic diagram illustrating the proposed mechanism of caveolin-1-mediated increase in invasion observed upon silencing FASN/ERα during hyperglycaemia-induced, matrix-specific EMT. Exposure to hyperglycaemia and fibronectin induces EMT and further enhances the Warburg effect by upregulating glucose uptake, lactate release and specific glycolytic enzymes and transporters. Inhibiting FASN/ERα signalling suppresses the glycolytic phenotype and promotes invasion via upregulation of caveolin-1 in lipid rafts also enriched in cholesterol and various signalling proteins and receptors. Considering the direct involvement of caveolin-1 in mediating cellular cholesterol homeostasis this pro-invasive phenotype is potentially associated with a metabolic shift from glycolysis to cholesterol biosynthetic pathway.