Oncotarget

Research Papers:

5-hydroxytryptamine receptor (5-HT1DR) promotes colorectal cancer metastasis by regulating Axin1/β-catenin/MMP-7 signaling pathway

Hua Sui, Hanchen Xu, Qing Ji, Xuan Liu, Lihong Zhou, Haiyan Song, Xiqiu Zhou, Yangxian Xu, Zhe-Sheng Chen, Guang Ji and Qi Li _

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Oncotarget. 2015; 6:25975-25987. https://doi.org/10.18632/oncotarget.4543

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Abstract

Hua Sui1,*, Hanchen Xu2,*, Qing Ji1, Xuan Liu1, Lihong Zhou1, Haiyan Song2, Xiqiu Zhou2, Yangxian Xu2, Zhesheng Chen3, Jianfeng Cai4, Guang Ji2, Qi Li1

1Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

2Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Chinese medicine, Shanghai 200032, China

3Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, Queens, NY 11439, USA

4Department of Chemistry, University of South Florida, Tampa, FL 33620, USA

*These authors have contributed equally to this work

Correspondence to:

Qi Li, e-mail: [email protected]

Guang Ji, e-mail: [email protected]

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

Received: March 24, 2015     Accepted: July 06, 2015     Published: July 17, 2015

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-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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