title: Dragon (RGMb) induces oxaliplatin resistance in colon cancer cells.
abstract: Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and a major cause of cancer mortality. Chemotherapy resistance remains a major challenge for treating advanced CRC. Therefore, the identification of targets that induce drug resistance is a priority for the development of novel agents to overcome resistance. Dragon (also known as RGMb) is a member of the repulsive guidance molecule (RGM) family. We previously showed that Dragon expression increases with CRC progression in human patients. In the present study, we found that Dragon inhibited apoptosis and increased viability of CMT93 and HCT116 cells in the presence of oxaliplatin. Dragon induced resistance of xenograft tumor to oxaliplatinin treatment in mice. Mechanistically, Dragon inhibited oxaliplatin-induced JNK and p38 MAPK activation, and caspase-3 and PARP cleavages. Our results indicate that Dragon may be a novel target that induces drug resistance in CRC.
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, China.
authors.forename: Xiao-Xiao
authors.initials: XX
authors.lastname: Huang
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, China.|Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, China.
authors.forename: Guo-Bin
authors.initials: GB
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhi
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, China.
authors.forename: Yuan-Sheng
authors.initials: YS
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, China.
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, China.
authors.forename: Li-Fen
authors.initials: LF
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, China.
authors.forename: Chuan-Xing
authors.initials: CX
authors.lastname: Xiao
authors.affiliation: Department of Basic Medical Sciences, Institute of Neuroscience, Medical College of Xiamen University, Xiamen, China.
authors.forename: Hui-Qin
authors.initials: HQ
authors.lastname: Xing
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, China.
authors.forename: Jian-Lin
authors.initials: JL
authors.lastname: Ren
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.|School of Biomedical Sciences Core Laboratory, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, China.|State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen, China.
authors.forename: Bayasi
authors.initials: B
authors.lastname: Guleng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D019006:Neural Cell Adhesion Molecules / Q000096:biosynthesis*; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D015816:Cell Adhesion Molecules, Neuronal; C484269:DRAGON protein, mouse; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D009944:Organoplatinum Compounds; C560433:RGMB protein, human; D000077150:Oxaliplatin
keywords: JNK; colon cancer; oxaliplatin resistance; p38 MAPK; Dragon