In cells expressing HIF-1α under hypoxic conditions or due to malfunctioning HIF-1α degradation signal, as in von-Hippel-Lindau (VHL) null renal carcinoma cells (RCC4), PKM2 has been shown to regulate the HIF-1α metabolic and angiogenic settings via enhancing HIF-1α binding to hypoxia response elements (HREs) within metabolic regulatory genes such as LDHA and PDK1 as well as VEGF [36]. Here, VHL is linked to renal carcinoma.