HIF1A and neoplasm: Lactate signaling induces HIF-1α-dependent polarization of macrophages and activates the lactate/HIF-1α/VEGF signaling axis, which upregulates the expression of the arginine metabolizing enzyme arginase 1 (Arg 1) to provide a substrate for cancer cell proliferation to support tumor growth and upregulates VEGF to induce neovascularization to achieve a tumor-promoting state (Chang et al., 2001; Qian and Pollard, 2010).