colorectal cancer, 5-hydroxytryptamine (5-HT) receptor, Wnt signaling pathway, metastasis, intestinal epithelium cells
Digital Object Identifier (DOI)
Overexpression of 5-hydroxytryptamine (5-HT) in human cancer contributes to tumor metastasis, but the role of 5-HT receptor family in cancer has not been thoroughly explored. Here, we report overexpression of 5-HT1D receptor (5-HT1DR) was associated with Wnt signaling pathway and advanced tumor stage. The underlying mechanism of 5-HT1DR-promoted tumor invasion was through its activation on the Axin1/β-catenin/MMP-7 pathway. In an orthotopic colorectal cancer mouse model, we demonstrated that a 5-HT1DR antagonist (GR127935) effectively inhibited tumor metastasis through targeting Axin1. Furthermore, in intestinal epithelium cells, we observed that 5-HT1DR played an important role in cell invasion via Axin1/β-catenin/MMP-7 pathway. Together, our findings reveal an essential role of the physiologic level of 5-HT1DR in pulmonary metastasis of colorectal cancer.
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Citation / Publisher Attribution
Oncotarget, v. 6, issue 28, p. 25975-25987
Scholar Commons Citation
Sui, Hua; Xu, Hanchen; Ji, Qing; Liu, Xuan; Zhou, Lihong; Song, Haiyan; Zhou, Xiqiu; Xu, Yangxian; Chen, Zhesheng; Cai, Jianfeng; Ji, Guang; and Li, Qi, "5-hydroxytryptamine Receptor (5-HT1DR) Promotes Colorectal Cancer Metastasis by Regulating Axin1/β-catenin/MMP-7 Signaling Pathway" (2015). Chemistry Faculty Publications. 126.