Oxytocin Alleviates Colitis and Colitis-Associated Colorectal Tumorigenesis via Noncanonical Fucosylation  

作　　者：Xia Wang Dawei Chen Mengnan Guo Yao Ning Mingze Geng Jing Guo Jiahui Gao Dong Zhao Yupeng Zhang Qianpeng Li Lixiang Li Shiyang Li Yanqing Li Xiaoran Xie Xiuli Zuo Jingxin Li 

机构地区：[1]Department of Gastroenterology,Qilu Hospital of Shandong University,Jinan,Shandong 250012,China [2]Laboratory of Translational Gastroenterology,Qilu Hospital of Shandong University,Jinan,Shandong 250012,China [3]Shandong Provincial Clinical Research Center for Digestive Disease,Jinan,Shandong 250012,China [4]Department of Physiology,School of Basic Medical Sciences,Cheeloo College of Medicine,Shandong University,Jinan,Shandong 250012,China [5]Department of Molecular Plant Biology,Norwegian Institute of Bioeconomy Research,Ås 1430,Norway [6]Department of Hematology,Weifang People's Hospital,Weifang,Shandong 261000,China [7]Advanced Medical Research Institute,Shandong University,Jinan,Shandong 250012,China

出　　处：《Research》2025年第1期593-605,共13页研究(英文)

基　　金：supported by the following grants:National Natural Science Foundation of China(82070551,82270570,32271172,and 82200584);China Postdoctoral Science Foundation(2022M721963);Taishan Scholars Program of Shandong Province,and the Natural Science Foundation of Shandong Province(ZR2021LSWO12).

摘　　要：Colon cancer is increasing worldwide and is commonly regarded as hormone independent,yet recent reports have implicated sex hormones in its development.Nevertheless,the role of hormones from the hypothalamus-hypophysis axis in colitis-associated colorectal cancer(CAC)remains uncertain.In this study,we observed a significant reduction in the expression of the oxytocin receptor(OXTR)in colon samples from both patient with colitis and patient with CAC.To investigate further,we generated mice with an intestinal-epithelium-cell-specific knockout of OXTR.These mice exhibited markedly increased susceptibility to dextran-sulfate-sodium-induced colitis and dextran sulfate sodium/azoxymethane-induced CAC compared to wild-type mice.Our findings indicate that OXTR depletion impaired the inner mucus of the colon epithelium.Mechanistically,oxytocin was found to regulate Mucin 2 maturation throughβ1-3-N-acetylglucosaminyltransferase 7(B3GNT7)-mediated fucosylation.Interestingly,we observed a positive correlation between B3GNT7 expression and OXTR expression in human colitis and CAC colon samples.Moreover,the simultaneous activations of OXTR and fucosylation by l-fucose significantly alleviated tumor burden.Hence,our study unveils oxytocin's promising potential as an affordable and effective therapeutic intervention for individuals affected by colitis and CAC.

关 键 词：sex hormones colon cancer FUCOSYLATION Colorectal Cancer generated mice OXYTOCIN COLITIS 

分 类 号：R574.62[医药卫生—消化系统]