Vascular endothelial growth factor D (VEGF-D) is a criticaal activator of tumor angiogenesis and lymphangiogenesis that recently has been implicated in the tumor metastasis process.In this study,we demonstrate that CD74 overexpression stimulated up-regulation of VEGF-D in human renal carcinoma cell lines.CD74-induced VEGF-D overexpression effectively promoted cancer cells and endothelial cells migration,proliferation and anchorage-independent growth.By way of investigating the upstream kinase pathway(s) involved in VEGF-D up-regulation,we found that CD74 not only activated extracellular signal-regulated protein kinase 1/2 (ERK 1/2) but also stimulated phosphatidylinositol 3-kinase (PI3K) through Syk signaling pathway.