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