机构：[1]Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.[2]Department of Laboratory Medicine, West China Hospital, Sichuan University, 610041 Chengdu, China.四川大学华西医院[3]Department of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland.[4]Departments of Chemistry and Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.[5]Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.[6]Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.[7]Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.[8]Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA.
Copper levels are known to be elevated in inflamed and malignant tissues. But the mechanism underlying this selective enrichment has been elusive. In this study, we report a axis by which inflammatory cytokines, such as IL-17, drive cellular copper uptake via the induction of a metalloreductase, STEAP4. IL-17-induced elevated intracellular copper level leads to the activation of an E3-ligase, XIAP, which potentiates IL-17-induced NFκB activation and suppresses the caspase 3 activity. Importantly, this IL-17-induced STEAP4-dependent cellular copper uptake is critical for colon tumor formation in a murine model of colitis-associated tumorigenesis and STEAP4 expression correlates with IL-17 level and XIAP activation in human colon cancer. In summary, this study reveals a IL-17-STEAP4-XIAP axis through which the inflammatory response induces copper uptake, promoting colon tumorigenesis.
基金：
This work was
supported by the National Institutes of Health grants (P01CA062220 and P01 HL103453
to X.L., R01CA193359 to M.F.K., GM 79465 to C.J.C. U01 CA 214300 and R01 237304 to E.H. and S10-OD019972 to the Imaging Core at the Lerner Institute at Cleveland Clinic)
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2020]版：
大类|1 区综合性期刊
小类|1 区综合性期刊
最新[2023]版：
大类|1 区综合性期刊
小类|1 区综合性期刊
第一作者：
第一作者机构：[1]Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.[2]Department of Laboratory Medicine, West China Hospital, Sichuan University, 610041 Chengdu, China.
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Liao Yun,Zhao Junjie,Bulek Katarzyna,et al.Inflammation mobilizes copper metabolism to promote colon tumorigenesis via an IL-17-STEAP4-XIAP axis.[J].Nature communications.2020,11(1):900.doi:10.1038/s41467-020-14698-y.
APA：
Liao Yun,Zhao Junjie,Bulek Katarzyna,Tang Fangqiang,Chen Xing...&Li Xiaoxia.(2020).Inflammation mobilizes copper metabolism to promote colon tumorigenesis via an IL-17-STEAP4-XIAP axis..Nature communications,11,(1)
MLA：
Liao Yun,et al."Inflammation mobilizes copper metabolism to promote colon tumorigenesis via an IL-17-STEAP4-XIAP axis.".Nature communications 11..1(2020):900
综合性期刊