Interleukin-6 Induces Vascular Endothelial Growth Factor-C Expression via Src-FAK-STAT3 Signaling in Lymphatic Endothelial CellsReport as inadecuate




Interleukin-6 Induces Vascular Endothelial Growth Factor-C Expression via Src-FAK-STAT3 Signaling in Lymphatic Endothelial Cells - Download this document for free, or read online. Document in PDF available to download.

Elevated serum interleukin-6 IL-6 levels correlates with tumor grade and poor prognosis in cancer patients. IL-6 has been shown to promote tumor lymphangiogenesis through vascular endothelial growth factor-C VEGF-C induction in tumor cells. We recently showed that IL-6 also induced VEGF-C expression in lymphatic endothelial cells LECs. However, the signaling mechanisms involved in IL-6-induces VEGF-C induction in LECs remain incompletely understood. In this study, we explored the causal role of focal adhesion kinase FAK in inducing VEGF-C expression in IL-6-stimulated murine LECs SV-LECs. FAK signaling blockade by NSC 667249 a FAK inhibitor attenuated IL-6-induced VEGF-C expression and VEGF-C promoter-luciferase activities. IL-6’s enhancing effects of increasing FAK, ERK1-2, p38MAPK, C-EBPβ, p65 and STAT3 phosphorylation as well as C-EBPβ-, κB- and STAT3-luciferase activities were reduced in the presence of NSC 667249. STAT3 knockdown by STAT3 siRNA abrogated IL-6’s actions in elevating VEGF-C mRNA and protein levels. Moreover, Src-FAK signaling blockade reduced IL-6’s enhancing effects of increasing STAT3 binding to the VEGF-C promoter region, cell migration and endothelial tube formation of SV-LECs. Together these results suggest that IL-6 increases VEGF-C induction and lymphangiogenesis may involve, at least in part, Src-FAK-STAT3 cascade in LECs.



Author: Yu-Han Huang , Hung-Yu Yang , Shiu-Wen Huang, George Ou, Ya-Fen Hsu , Ming-Jen Hsu

Source: http://plos.srce.hr/



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