title: 5-hydroxytryptamine receptor (5-HT1DR) promotes colorectal cancer metastasis by regulating Axin1/β-catenin/MMP-7 signaling pathway.
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(1D)R) was associated with Wnt signaling pathway and advanced tumor stage. The underlying mechanism of 5-HT(1D)R-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(1D)R antagonist (GR127935) effectively inhibited tumor metastasis through targeting Axin1. Furthermore, in intestinal epithelium cells, we observed that 5-HT(1D)R 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(1D)R in pulmonary metastasis of colorectal cancer.
authors.affiliation: Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Sui
authors.affiliation: Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Chinese Medicine, Shanghai 200032, China.
authors.forename: Hanchen
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ji
authors.affiliation: Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Chinese Medicine, Shanghai 200032, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Song
authors.affiliation: Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Chinese Medicine, Shanghai 200032, China.
authors.forename: Xiqiu
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Chinese Medicine, Shanghai 200032, China.
authors.forename: Yangxian
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA.
authors.forename: Zhesheng
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Chemistry, University of South Florida, Tampa, FL 33620, USA.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Cai
authors.affiliation: Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Chinese Medicine, Shanghai 200032, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Ji
authors.affiliation: Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
mesh_terms: D000818:Animals; D060466:Axin Protein / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism*; D008819:Mice, Nude; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010069:Oxadiazoles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D044346:Receptor, Serotonin, 5-HT1D / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012702:Serotonin Antagonists / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D047368:Tumor Burden / Q000187:drug effects / Q000235:genetics; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C555451:AXIN1 protein, human; D060466:Axin Protein; D010069:Oxadiazoles; D010879:Piperazines; D044346:Receptor, Serotonin, 5-HT1D; D012702:Serotonin Antagonists; D051176:beta Catenin; C090701:GR 127935; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7
keywords: 5-hydroxytryptamine (5-HT) receptor; Wnt signaling pathway; colorectal cancer; intestinal epithelium cells; metastasis