The oncogenic role of Wnt10a in colorectal cancer through activation of canonical Wnt/β-catenin signaling

摘要

Colorectal cancer (CRC) is one of the major causes of cancer-associated mortality worldwide. Wnt family member 10A (Wnt10a) is an oncogene associated with the carcinogenesis and progression of renal cell carcinoma, and is strongly expressed in the CRC cell line SW480. However, the role of Wnt10a in CRC has been rarely reported. In the present study, the expression levels of Wnt10a were higher in 40 tumor tissues compared with in paired control tissues, as determined by RT-qPCR method. In addition, the clinic opathological association analysis indicated that Wnt10a expression was associated with tumor stage (T3+T4, P=0.015). Furthermore, Wnt10a was highly expressed in the SW480, SW620 and HCT116 cell lines. In order to explore the role of Wnt10a in CRC, Wnt10a expression was knocked down by siRNA technology in HCT116 cell line. Cell proliferation was significantly inhibited by 55% in CCK-8 assay following Wnt10a knockdown and cell migration rate was decreased by 50% in Transwell assay. In addition, western blot analysis demonstrated that Wnt10a knockdown decreased the expression levels of β-catenin, cyclin D1, lymphoid enhancer-binding factor 1 and protein kinase B, which was consistent with results obtained with the Wnt/β-catenin specific inhibitor LGK-974. It was thus suggested that Wnt10a downregulation inactivated the Wnt/β-catenin signaling pathway in HCT116 cells. In conclusion, the present study demonstrated that Wnt10a may have an oncogenic role during carcinogenesis of CRC through activation of Wnt/β-catenin signaling.