TRAF6 promoted the tumorigenicity of esophageal squamous cell carcinoma
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide. It is very urgent to understand the underlying molecular mechanism and develop new therapeutic strategy. Tumor necrosis factor receptor-associated factor (TRAF6), initially identified as a regulator of NF-κB, recently has been found to be involved in cancer by modulating various signaling pathways. However, the function of TRAF6 in ESCC is poorly understood. Here, we found that the expression of TRAF6 was upregulated in ESCC cell lines and clinical samples. Moreover, over-expression of TRAF6 in ESCC cells promoted cell proliferation, while downregulation of TRAF6 impaired the tumorigenicity of ESCC cells in vitro and in vivo. Mechanistically, TRAF6 inhibited cell apoptosis by downregulation of activated caspase 3 and cleaved poly ADP ribose polymerase and upregulation of c-Jun, Bcl2, and c-Myc. Taken together, our study suggested the oncogenic role of TRAF6 in ESCC, and TRAF6 might be an important therapeutic target for ESCC.
- Toh Y, Oki E, Ohgaki K, et al. Alcohol drinking, cigarette smoking, and the development of squamous cell carcinoma of the esophagus: molecular mechanisms of carcinogenesis. Int J Clin Oncol. 2010;15:135–44. CrossRef
- Zhou ZQ, Cao WH, Xie JJ, et al. Expression and prognostic significance of THBS1, Cyr61 and CTGF in esophageal squamous cell carcinoma. BMC Cancer. 2009;9:291–7. CrossRef
- Yoshinaga K, Yamashita K, Mimori K, Tanaka F, Inoue H, Mori M. Activin a causes cancer cell aggressiveness in esophageal squamous cell carcinoma cells. Ann Surg Oncol. 2008;15(1):96–103. CrossRef
- Inoue J, Gohda J, Akiyama T. Characteristics and biological functions of TRAF6. Adv Exp Med Biol. 2007;597:72–9. CrossRef
- Daniel TS, William WL, Sophie D. TRAF6 is an amplified oncogene bridging the RAS and NF-κB pathways in human lung cancer. J Clin Invest. 2011;121(10):4095–105. CrossRef
- Hirata Y, Ohmae T, Shibata W, et al. MyD88 and TNF receptor-associated factor 6 are critical signal transducers in Helicobacter pylori-infected human epithelial cells. J Immunol. 2006;176(6):3796–803.
- Bradley JR, Pober JS. Tumor necrosis factor receptor-associated factors (TRAFs). Oncogene. 2001;20(44):6482–91. CrossRef
- Yang WL, Wang J, Chan CH, et al. The E3 ligase TRAF6 regulates Akt ubiquitination and activation. Science. 2009;325:1134–8. CrossRef
- Zhang W, Chen H, Liu DL, et al. Emodin sensitizes the gemcitabine-resistant cell line Bxpc-3/Gem to gemcitabine via downregulation of NF-κB and its regulated targets. Int J Oncol. 2013;42(4):1189–96.
- Bastian L, Hof J, Pfau M, et al. Synergistic activity of bortezomib and HDACi in preclinical models of B-cell precursor acute lymphoblastic leukemia via modulation of p53, PI3K/AKT, and NF-κB. Clin Cancer Res. 2013;19(6):1445–57. CrossRef
- Peinado C, Kang X, Hardamon C, et al. (2013) The NF-κB pathway down-regulates expression of the NKG2D ligand H60a in vitro: implications for use of NF-κB inhibitors in cancer therapy. Immunology doi:10.1111/imm.12080.
- Wang F, He W, Fanghui P, et al. (2013) NF-kappa BP65 promotes invasion and metastasis of esophageal squamous cell cancer by regulating matrix metalloproteinase-9 and epithelial-to-mesenchymal transition. Cell Biol Int doi:10.1002/cbin.10089.
- TRAF6 promoted the tumorigenicity of esophageal squamous cell carcinoma
Volume 34, Issue 5 , pp 3201-3207
- Cover Date
- Print ISSN
- Online ISSN
- Springer Netherlands
- Additional Links
- Cell growth and apoptosis
- Industry Sectors
- Author Affiliations
- 1. Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Rd, Shanghai, 200030, China
- 2. Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, 174 Changhai Rd, Shanghai, 200433, China