Figure 6:

In this illustration, potential mechanisms of tumor cell survival via crosstalk between components of the MET pathway, glycolysis, and autophagy are depicted. Basal levels of autophagy are typically low through mTOR inhibition of ULK1, a key enzyme in upregulation of autophagy, and glycolysis predominates as the main mechanism for ATP generation. Aberrant MET activation leads to upregulation of downstream effectors including components of the PI3K/AKT/mTOR pathway and glycolytic metabolism is maintained. Through blockade of MET and subsequent indirect activation of ULK1 through the absence of negative feedback with mTOR inhibition, upregulation in autophagy occurs to maintain cellular homeostasis. A simplified canonical pathway of autophagy (steps 1–4) are shown.