As an important part of cancer cell metastasis, AMPK activation can be induced by EPH receptor A2 (EPHA2)-enriched exosomes via a canonical forward signaling pathway that is dependent upon the ligand Ephrin A1, indicating that EPHA2, Ephrin A1, and HIF-1α, which are specifically contained in the tumor microenvironment, jointly promote AMPK activation and angiogenesis [118]. This evidence concerns the gene PRKAA2 and cancer.