Knockdown of YKL‐40 inhibits angiogenesis through regulation of VEGF/VEGFR2 and ERK1/2 signaling in endometrial cancer

Abstract Studies have demonstrated that small interfering RNA (siRNA) targeting YKL‐40 (si YKL‐40 ) inhibits the proliferation, migration, invasion, and induces antiapoptotic abilities of endometrial cancer (EC) HEC‐1A cells. However, its effect on angiogenesis is unclear. The present study aimed to investigate the role of YKL‐40 in endometrial cancer and the related molecular mechanisms. YKL‐40 was knocked down by transfection with si YKL‐40 and the effects on angiogenesis, cell viability, and signaling pathways were investigated. The results showed that si YKL‐40 inhibited VEGFA levels and tube formation in endothelial cells. Additionally, inhibition of YKL‐40 decreased the expression levels of vascular endothelial growth factor (VEGF), phosphorylated vascular endothelial growth factor receptor 2 (pVEGFR2), and phosphorylated extracellular signal‐regulated kinases 1 and 2 (pERK1/2). Furthermore, a nude mice xenograft model of EC showed that si YKL‐40 inhibited tumor growth. Inhibition of YKL‐40 led to suppression of angiogenesis and reduction of microvessel density through VEGF/VEGFR2 and ERK1/2 signaling in endometrial cancer cells. Taken together, this study demonstrated novel molecular mechanisms for role of YKL‐40 in EC.