title: TRAF6 promoted the metastasis of esophageal squamous cell carcinoma.
abstract: Esophageal cancer is one of the most aggressive malignancies and has been ranked as the sixth leading cause of cancer-related death in the world. It is very urgent to find new therapeutic targets. Although tumor necrosis factor receptor-associated factor 6 (TRAF6) was initially identified as an adaptor for NF-κB signaling, recently it has been found to be involved in cancer by modulating various signaling pathways. In the previous study, we have found that TRAF6 promoted the growth of esophageal squamous cell carcinoma (ESCC) cell in vitro and in vivo. However, the effects of TRAF6 on the migration and metastasis of ESCC cells are poorly understood. Here, we found that TRAF6 promoted migration and metastasis of ESCC cells through modulating Ras signaling. Overexpression of TRAF6 promoted the migration of ESCC cells and immortalized esophageal epithelial cells, while knock down the expression of TRAF6 inhibited the migration and metastasis of ESCC cells in vitro and in vivo. Mechanically, TRAF6 binds Ras with its N-terminal and activated Ras signaling. Taken together, TRAF6 played an important role in the metastasis of ESCC and might be a promising therapeutic target.
authors.affiliation: Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, 174 Changhai Rd, Shanghai, 200433, China, handoctor@gmail.com.
authors.forename: Qingqi
authors.initials: Q
authors.lastname: Han
authors.forename: Feng
authors.initials: F
authors.lastname: Yao
authors.forename: Chenxi
authors.initials: C
authors.lastname: Zhong
authors.forename: Heng
authors.initials: H
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D004195:Disease Models, Animal; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D064593:Heterografts; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics* / Q000378:metabolism
chemical_list: D048029:TNF Receptor-Associated Factor 6; D048049:Extracellular Signal-Regulated MAP Kinases; D016283:Proto-Oncogene Proteins p21(ras)
references.citation: Eur J Cancer. 2001 Oct;37 Suppl 8:S4-66
references.pmid: 11602373
references.citation: J Biol Chem. 2012 Mar 30;287(14):11002-10
references.pmid: 22262844
references.citation: Cancer Cell. 2004 Oct;6(4):313-9
references.pmid: 15488754
references.citation: Hepatology. 2011 Feb;53(2):483-92
references.pmid: 21274870
references.citation: Am J Hum Genet. 2000 Jul;67(1):110-9
references.pmid: 10841811
references.citation: Adv Exp Med Biol. 2007;597:72-9
references.pmid: 17633018
references.citation: J Biol Chem. 2012 Aug 17;287(34):29114-24
references.pmid: 22773835
references.citation: CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66
references.pmid: 17237035
references.citation: J Biol Chem. 2012 Jan 2;287(1):123-133
references.pmid: 22069318
references.citation: Carcinogenesis. 2004 Apr;25(4):527-33
references.pmid: 14688025
references.citation: J Clin Invest. 2011 Oct;121(10):4095-105
references.pmid: 21911935
references.citation: Pathol Oncol Res. 2008 Sep;14(3):267-73
references.pmid: 18592405
references.citation: Cancer Epidemiol Biomarkers Prev. 2008 Dec;17(12):3593-602
references.pmid: 19064576
references.citation: Nat Immunol. 2012 Sep;13(9):823-31
references.pmid: 22863753
references.citation: Cancer Sci. 2009 Sep;100(9):1591-6
references.pmid: 19552757
references.citation: N Engl J Med. 2003 Dec 4;349(23):2241-52
references.pmid: 14657432