Fig. 8: Schematic diagram of the effect of HIF2α-MCJ on the secretion of legumain and subsequently promoting tumor metastasis of ccRCC.

HIF2α transcriptionally activates MCJ, leading to mitochondrial damage. The excessive accumulation of mtROS enhances the oxidation sites and secretion of prolegumain. Once extracellular, legumain influences the activation of MMP2, tumor invasion capacity, and angiogenesis, thereby playing a pro-metastatic role in ccRCC.