SPHK1 Promotes Pancreatic Cancer Lymphangiogenesis Through the Activation of ERK in LECs

Lymphatic metastasis is related to an unsatisfactory prognosis in pancreatic cancer. Sphingosine kinase 1 (SPHK1) is an oncogene in cancer. However, the potential effect of SPHK1 on the lymphangiogenesis of pancreatic cancer is little known. In this study, the expression level and role of SPHK1 in pancreatic cancer were evaluated to explore the underlying mechanism involved. The expression of SPHK1 and the lymphatic vessel density (LVD) in pancreatic cancer patient tissue were investigated by immunohistochemistry. The role of SPHK1 in lymphangiogenesis was verified in vitro. Elevated expression of SPHK1 was strongly related to high LVD in pancreatic cancer patient tissue. Silencing of SPHK1 in pancreatic cancer cells observably inhibited lymphangiogenesis. Furthermore, the downregulation of SPHK1 markedly attenuated the phosphorylation of extracellular signal-regulated kinase in lymphatic endothelial cells. This study revealed that SPHK1 might play a crucial role in pancreatic cancer lymphangiogenesis.