Fig. 4. YAP/TAZ bridges the influences of ECM and TGF-β.

YAP/TAZ localizes to the nucleus upon stiff ECM where it stabilizes the Smad complex and sustains the gene expression observed for TGF-β. Moreover, YAP/TAZ can also independently promote glycolysis and glutaminolysis by increasing the expression of glucose transporters (GLUTs), of phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and of glutamine synthesis (GLS1) for the collagen production. As a consequence, increased sterol and fatty acid levels promote more Rho expression and thereby promote a feedforward loop. AMPK AMP-activated protein kinase, mTOR mammalian target of rapamycin, PFK phosphofructokinase.