STAT3 and neoplasm: Tumor‐derived legumain interacts with endothelial integrin αvβ3 through its Arg‐Gly‐Asp (RGD) motif and indirectly downregulates the expression of zonula occludens 1 via the STAT3 signaling pathway, which can promote tumor metastasis by increasing the permeability of endothelial barriers [111, 112].