Figure 1. The proposed mechanism of KRASG12D-induced lymphangiogenesis in PDAC.
PDAC cells with the KRASG12D mutation upregulate SAE1, which triggers SUMOylation. Subsequent SUMOylation of hnRNPA1 at lysine 113 enables interaction with a component of the endosomal sorting complex, TSG101. EVs are loaded with SUMOylated hnRNPA1 and released into the tumor microenvironment. Local lymphatic endothelial cells internalizing EVs via endocytosis acquire elevated SUMOylated hnRNPA1, stabilizing PROX1 mRNA to increase PROX1 expression and lymphangiogenesis.