Fig. 6
From: AXL signaling in cancer: from molecular insights to targeted therapies

AXL alters glucose metabolism to develop acquired resistance in cancer cells. AXL-GAS6 signaling promotes glycolysis through multiple pathways, reducing sensitivity to cytotoxic stress and fostering chemoresistance. AXL-mediated PI3K/Akt signaling activates glycolysis. After AXL phosphorylates TNS2 at Y483, TNS2 becomes more stable and disengages from IRS-1. The overexpression of GLUT4 and PDK1, resulting from AXL/TNS2/IRS-1 crosstalk, enhances related metabolism. Additionally, AXL phosphorylates PKM2 at Y105, reducing its ability to bind phosphoenolpyruvate and further promoting glycolysis