夏普
癌变
癌症研究
炎症
化学
细胞凋亡
细胞生物学
医学
生物
生物化学
免疫学
程序性细胞死亡
半胱氨酸蛋白酶
基因
作者
Yun Liao,Junjie Zhao,Katarzyna Bulek,Fangqiang Tang,Xing Chen,Gang Cai,Shang Jia,Paul L. Fox,Emina H. Huang,Theresa T. Pizarro,Matthew F. Kalady,Mark W. Jackson,Shideng Bao,Ganes C. Sen,George R. Stark,Christopher J. Chang,Xiaoxia Li
标识
DOI:10.1038/s41467-020-14698-y
摘要
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.
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