EPAS1 and neoplasm: In an anaerobic environment, lactate produced by tumor cells inhibits the expression of the macrophage-specific vacuolar ATPase subunit ATP6V0d2 by stimulating the microtubule-targeting chimera 1 (mTOC1) pathway; this results in an elevation in the HIF-2α-mediated production of VEGF in macrophages, which subsequently display tumor-cell growth-promoting characteristics [63].