دورية أكاديمية
RNF186/EPHB2 Axis Is Essential in Regulating TNF Signaling for Colorectal Tumorigenesis in Colorectal Epithelial Cells.
| العنوان: | RNF186/EPHB2 Axis Is Essential in Regulating TNF Signaling for Colorectal Tumorigenesis in Colorectal Epithelial Cells. |
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| المؤلفون: | Zhang H; Key Laboratory of Molecular Biophysics of the Ministry of Education, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China., Cui Z; Key Laboratory of Molecular Biophysics of the Ministry of Education, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China., Pan T; The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.; Research Unit for Blindness Prevention of the Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China; and., Hu H; Key Laboratory of Molecular Biophysics of the Ministry of Education, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China., He R; The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.; Research Unit for Blindness Prevention of the Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China; and., Yi M; The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.; Research Unit for Blindness Prevention of the Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China; and., Sun W; Key Laboratory of Molecular Biophysics of the Ministry of Education, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China., Gao R; Key Laboratory of Molecular Biophysics of the Ministry of Education, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China., Wang H; Key Laboratory of Molecular Biophysics of the Ministry of Education, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China., Ma X; Key Laboratory of Molecular Biophysics of the Ministry of Education, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China., Peng Q; Key Laboratory of Molecular Biophysics of the Ministry of Education, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China., Feng X; Key Laboratory of Molecular Biophysics of the Ministry of Education, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China., Liang S; Wuhan Biobank Co., Ltd., Wuhan, China., Du Y; The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China; yanyundu1@163.com wangch@uestc.edu.cn.; Research Unit for Blindness Prevention of the Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China; and., Wang C; The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China; yanyundu1@163.com wangch@uestc.edu.cn.; Research Unit for Blindness Prevention of the Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China; and. |
| المصدر: | Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2022 Nov 01; Vol. 209 (9), pp. 1796-1805. Date of Electronic Publication: 2022 Sep 21. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association of Immunologists Country of Publication: United States NLM ID: 2985117R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1550-6606 (Electronic) Linking ISSN: 00221767 NLM ISO Abbreviation: J Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Bethesda, MD : American Association of Immunologists Original Publication: Baltimore : Williams & Wilkins, c1950- |
| مواضيع طبية MeSH: | Colorectal Neoplasms*/genetics , Receptor, EphA1*/metabolism, Animals ; Humans ; Mice ; Carcinogenesis ; Cytokines ; Epithelial Cells/metabolism ; Signal Transduction ; Tyrosine ; Ubiquitin/metabolism ; Ubiquitin-Protein Ligases/genetics ; Ubiquitin-Protein Ligases/metabolism ; Receptor, EphB2 |
| مستخلص: | The receptor tyrosine kinase EPHB2 (EPH receptor B2) is highly expressed in many human cancer types, especially in gastrointestinal cancers, such as colorectal cancer. Several coding mutations of the EPHB2 gene have been identified in many cancer types, suggesting that EPHB2 plays a critical role in carcinogenesis. However, the exact functional mechanism of EPHB2 in carcinogenesis remains unknown. In this study, we find that EPHB2 is required for TNF-induced signaling activation and proinflammatory cytokine production in colorectal epithelial cells. Mechanistically, after TNF stimulation, EPHB2 is ubiquitinated by its E3 ligase RNF186. Then, ubiquitinated EPHB2 recruits and further phosphorylates TAB2 at nine tyrosine sites, which is a critical step for the binding between TAB2 and TAK1. Due to defects in TNF signaling in RNF186-knockout colorectal epithelial cells, the phenotype of colitis-propelled colorectal cancer model in RNF186-knockout mice is significantly reduced compared with that in wild-type control mice. Moreover, we find that a genetic mutation in EPHB2 identified in a family with colorectal cancer is a gain-of-function mutation that promoted TNF signaling activation compared with wild-type EPHB2. We provide evidence that the EPHB2-RNF186-TAB2-TAK1 signaling cascade plays an essential role in TNF-mediated signal transduction in colorectal epithelial cells and the carcinogenesis of colorectal cancer, which may provide potential targets for the treatment of colorectal cancer. (Copyright © 2022 by The American Association of Immunologists, Inc.) |
| References: | Cell. 2002 Oct 18;111(2):251-63. (PMID: 12408869) Front Biosci. 2008 May 01;13:5094-107. (PMID: 18508572) Mol Cell. 2004 Aug 27;15(4):535-48. (PMID: 15327770) Nat Genet. 2007 Nov;39(11):1376-83. (PMID: 17906625) Cell Prolif. 2013 Aug;46(4):374-81. (PMID: 23869759) PLoS Genet. 2013;9(9):e1003723. (PMID: 24068945) J Biol Chem. 2007 Jun 8;282(23):16776-82. (PMID: 17449468) Oncogene. 2015 Jul;34(27):3493-503. (PMID: 25174402) Cell. 2006 Jun 16;125(6):1151-63. (PMID: 16777604) Cell. 2000 Dec 8;103(6):945-56. (PMID: 11136979) Nat Rev Cancer. 2010 Mar;10(3):165-80. (PMID: 20179713) Annu Rev Pharmacol Toxicol. 2015;55:465-87. (PMID: 25292427) Genes Dev. 1999 Feb 1;13(3):295-306. (PMID: 9990854) Nature. 2005 Jun 23;435(7045):1126-30. (PMID: 15973414) Oncogene. 2007 Mar 1;26(10):1385-97. (PMID: 16953224) Carcinogenesis. 2012 Apr;33(4):931-6. (PMID: 22354874) Gastroenterology. 2010 Jun;138(6):2101-2114.e5. (PMID: 20420949) Nat Commun. 2020 Apr 20;11(1):1913. (PMID: 32312989) Cell. 2009 Nov 13;139(4):679-92. (PMID: 19914164) World J Gastroenterol. 2005 Mar 21;11(11):1639-43. (PMID: 15786541) Nat Genet. 2004 Sep;36(9):979-83. (PMID: 15300251) Autophagy. 2021 Oct;17(10):3030-3047. (PMID: 33280498) Cell. 2008 Apr 4;133(1):38-52. (PMID: 18394988) J Cell Biol. 2003 Dec 22;163(6):1313-26. (PMID: 14691139) Cancer Res. 2005 Nov 15;65(22):10170-3. (PMID: 16288001) Clin Cancer Res. 2005 Sep 15;11(18):6450-8. (PMID: 16166419) Science. 2002 May 31;296(5573):1634-5. (PMID: 12040173) Cancer Res. 2004 Feb 1;64(3):781-8. (PMID: 14871799) J Biol Chem. 2005 Dec 30;280(52):43056-63. (PMID: 16260783) Cell Stem Cell. 2011 May 6;8(5):511-24. (PMID: 21419747) J Clin Invest. 2008 Feb;118(2):560-70. (PMID: 18219394) Trends Cell Biol. 2001 Sep;11(9):372-7. (PMID: 11514191) |
| المشرفين على المادة: | 0 (Cytokines) EC 2.7.10.1 (Receptor, EphA1) EC 2.3.2.27 (RNF186 protein, human) 42HK56048U (Tyrosine) 0 (Ubiquitin) EC 2.3.2.27 (Ubiquitin-Protein Ligases) EC 2.7.10.1 (Receptor, EphB2) |
| تواريخ الأحداث: | Date Created: 20220921 Date Completed: 20221021 Latest Revision: 20221205 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC9553791 |
| DOI: | 10.4049/jimmunol.2200229 |
| PMID: | 36130827 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1550-6606 |
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| DOI: | 10.4049/jimmunol.2200229 |