Heat shock protein 90-extracellular regulated protein kinases-vascular endothelial growth factor signaling induces vascular cells migration and angiogenesis in colorectal cancer

Abstract

Objective To explore whether heat shock protein 90 (HSP90)-extracellular regulated protein kinases (ERK)-vascular endothelial growth factor (VEGF) signaling could induce vascular cells migration and angiogenesis in colorectal cancer and underlying mechanisms.Methods The expression of VEGF in colorectal cancer and adjacent normal tissue was detected by Western blotting.Wound healing and tube formation asssay were applied to evaluate the angiogenesis ability of human umbilical vein endothelial cells (HUVECS) in the conditional medium collected from colorectal cancer cell line (HCT116).Results VEGF expression level was higher in fresh colorectal cancer tissues compared with adjacent normal tissues in the patients of stage Ⅱ,Ⅲ,Ⅳ.HSP90 activates phosphorylation of ERK to induce the expression of secretory VEGF in HCT116,thus enhancing the migration and tube formation ability of HUVECS in the conditional medium.Enhanced angiogenesis activity was partially reversed by U0126 treatment.Conclusion HSP90-ERK-VEGF pathway plays an important role in angiogenesis of colorectal cancer. Key words: Colorectal cancer; Heat shock protein 90; Extracellular regulated protein kinases; Vascular endothelial growth factor; Angiogenesis