5-hydroxytryptamine Receptor (5-HT_1DR) Promotes Colorectal Cancer Metastasis by Regulating Axin1/β-catenin/MMP-7 Signaling Pathway

Authors

Hua Sui, Shanghai University of Traditional Chinese Medicine
Hanchen Xu, Shanghai University of Chinese medicine
Qing Ji, Shanghai University of Traditional Chinese Medicine
Xuan Liu, Shanghai University of Traditional Chinese Medicine
Lihong Zhou, Shanghai University of Traditional Chinese Medicine
Haiyan Song, Shanghai University of Chinese medicine
Xiqiu Zhou, Shanghai University of Chinese medicine
Yangxian Xu, Shanghai University of Chinese medicine
Zhesheng Chen, St. John’s University
Jianfeng Cai, University of South FloridaFollow
Guang Ji, Shanghai University of Chinese medicine
Qi Li, Shanghai University of Traditional Chinese Medicine

Document Type

Article

Publication Date

2015

Keywords

colorectal cancer, 5-hydroxytryptamine (5-HT) receptor, Wnt signaling pathway, metastasis, intestinal epithelium cells

Digital Object Identifier (DOI)

https://doi.org/10.18632/oncotarget.4543

Abstract

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-HT_1D receptor (5-HT_1DR) was associated with Wnt signaling pathway and advanced tumor stage. The underlying mechanism of 5-HT_1DR-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-HT_1DR antagonist (GR127935) effectively inhibited tumor metastasis through targeting Axin1. Furthermore, in intestinal epithelium cells, we observed that 5-HT_1DR 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-HT_1DR in pulmonary metastasis of colorectal cancer.

Rights Information

This work is licensed under a Creative Commons Attribution 3.0 License.

Was this content written or created while at USF?

Yes

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-HT_1DR) Promotes Colorectal Cancer Metastasis by Regulating Axin1/β-catenin/MMP-7 Signaling Pathway" (2015). Chemistry Faculty Publications. 126.
https://digitalcommons.usf.edu/chm_facpub/126