Skip to main content
SpringerLink
Log in

RETRACTED ARTICLE: TNF receptor-associated factor 6 regulates proliferation, apoptosis, and invasion of glioma cells

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

This article was retracted on 18 March 2016

Abstract

Tumor necrosis factor receptor-associated factor 6 (TRAF6), which plays an important role in inflammation and immune response, is an essential adaptor protein for the NF-κB (nuclear factor κB) signaling pathway. Recent studies have shown that TRAF6 played an important role in tumorigenesis and invasion by suppressing NF-κB activation. However, up to now, the biologic role of TRAF6 in glioma has still remained unknown. To address the expression of TRAF6 in glioma cells, four glioma cell lines (U251, U-87MG, LN-18, and U373) and a non-cancerous human glial cell line SVG p12 were used to explore the protein expression of TRAF6 by Western blot. Our results indicated that TRAF6 expression was upregulated in human glioma cell lines, especially in metastatic cell lines. To investigate the role of TRAF6 in cell proliferation, apoptosis, invasion, and migration of glioma, we generated human glioma U-87MG cell lines in which TRAF6 was either overexpressed or depleted. Subsequently, the effects of TRAF6 on cell viability, cell cycle distribution, apoptosis, invasion, and migration in U-87MG cells were determined with 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl tetrazolium bromide (MTT) assay, flow cytometry analysis, transwell invasion assay, and wound-healing assay. The results showed that knockdown of TRAF6 could decrease cell viability, suppress cell proliferation, invasion and migration, and promote cell apoptosis, whereas overexpression of TRAF6 displayed the opposite effects. In addition, the effects of TRAF6 on the expression of phosphor-NF-κB (p-p65), cyclin D1, caspase 3, and MMP-9 were also probed. Knockdown of TRAF6 could lower the expression of p-p65, cyclin D1, and MMP-9, and raise the expression of caspase 3. All these results suggested that TRAF6 might be involved in the potentiation of growth, proliferation, invasion, and migration of U-87MG cell, as well as inhibition of apoptosis of U-87MG cell by abrogating activation of NF-κB.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Farias-Eisner G, Bank AM, Hwang BY, Appelboom G, Piazza MA, Bruce SS, Sander Connolly E (2012) Glioblastoma biomarkers from bench to bedside: advances and challenges. Br J Neurosurg 26:189–194

    Article  PubMed  Google Scholar 

  2. Walecki J, Tarasow E, Kubas B, Czemicki Z, Lewko J, Podgorski J, Sokol M, Grieb P (2003) Hydrogen-1 MR spectroscopy of the peritumoral zone in patients with cerebral glioma: assessment of the value of the method. Acad Radiol 10:145–153

    Article  PubMed  Google Scholar 

  3. Ferguson SD (2011) Malignant gliomas: diagnosis and treatment. Dis Mon 57:558–569

    Article  PubMed  Google Scholar 

  4. Rainov NG, Heidecke V (2011) Clinical development of experimental therapies for malignant glioma. Sultan Qaboos Univ Med J 11:5–28

    PubMed  PubMed Central  Google Scholar 

  5. Yamanaka R, Kajiwara K (2012) Dendritic cell vaccines. Adv Exp Med Biol 746:187–200

    Article  CAS  PubMed  Google Scholar 

  6. Jin HR, Jin SZ, Cai XF, Li D, Wu X, Nan JX, Lee JJ, Jin X (2012) Cryptopleurine targets NF-kappaB pathway, leading to inhibition of gene products associated with cell survival, proliferation, invasion, and angiogenesis. PLoS One 7:e40355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Liu YQ, Hu XY, Lu T, Cheng YN, Young CY, Yuan HQ, Lou HX (2012) Retigeric acid B exhibits antitumor activity through suppression of nuclear factor-kappaB signaling in prostate cancer cells in vitro and in vivo. PLoS One 7:e38000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kang K, Lim JS (2012) Induction of functional changes of dendritic cells by silica nanoparticles. Immune Netw 12:104–112

    Article  PubMed  PubMed Central  Google Scholar 

  9. Prasad S, Yadav VR, Sung B, Reuter S, Kannappan R, Deorukhkar A, Diagaradjane P, Wei C, Baladandayuthapani V, Krishnan S et al (2012) Ursolic acid inhibits growth and metastasis of human colorectal cancer in an orthotopic nude mouse model by targeting multiple cell signaling pathways: chemosensitization with capecitabine. Clin Cancer Res 18:4942–4953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ge Y, Xu Y, Sun W, Man Z, Zhu L, Xia X, Zhao L, Zhao Y, Wang X (2012) The molecular mechanisms of the effect of dexamethasone and cyclosporin A on TLR4/NF-kappaB signaling pathway activation in oral lichen planus. Gene 508:157–164

    Article  CAS  PubMed  Google Scholar 

  11. Jia L, Gopinathan G, Sukumar JT, Gribben JG (2012) Blocking autophagy prevents bortezomib-induced NF-kappaB activation by reducing I-kappaBalpha degradation in lymphoma cells. PLoS One 7:e32584

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Gupta SC, Sundaram C, Reuter S, Aggarwal BB (2010) Inhibiting NF-kappaB activation by small molecules as a therapeutic strategy. Biochim Biophys Acta 1799:775–787

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Tsuchiya Y, Asano T, Nakayama K, Kato T Jr, Karin M, Kamata H (2010) Nuclear IKKbeta is an adaptor protein for IkappaBalpha ubiquitination and degradation in UV-induced NF-kappaB activation. Mol Cell 39:570–582

    Article  CAS  PubMed  Google Scholar 

  14. Tao T, Cheng C, Ji Y, Xu G, Zhang J, Zhang L, Shen A (2012) Numbl inhibits glioma cell migration and invasion by suppressing TRAF5-mediated NF-kappaB activation. Mol Biol Cell 23:2635–2644

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Tran NL, McDonough WS, Savitch BA, Fortin SP, Winkles JA, Symons M, Nakada M, Cunliffe HE, Hostetter G, Hoelzinger DB et al (2006) Increased fibroblast growth factor-inducible 14 expression levels promote glioma cell invasion via Rac1 and nuclear factor-kappaB and correlate with poor patient outcome. Cancer Res 66:9535–9542

    Article  CAS  PubMed  Google Scholar 

  16. Sarkar D, Park ES, Emdad L, Lee SG, Su ZZ, Fisher PB (2008) Molecular basis of nuclear factor-kappaB activation by astrocyte elevated gene-1. Cancer Res 68:1478–1484

    Article  CAS  PubMed  Google Scholar 

  17. Sung B, Pandey MK, Nakajima Y, Nishida H, Konishi T, Chaturvedi MM, Aggarwal BB (2008) Identification of a novel blocker of IkappaBalpha kinase activation that enhances apoptosis and inhibits proliferation and invasion by suppressing nuclear factor-kappaB. Mol Cancer Ther 7:191–201

    Article  CAS  PubMed  Google Scholar 

  18. Ichikawa H, Takada Y, Murakami A, Aggarwal BB (2005) Identification of a novel blocker of I kappa B alpha kinase that enhances cellular apoptosis and inhibits cellular invasion through suppression of NF-kappa B-regulated gene products. J Immunol 174:7383–7392

    Article  CAS  PubMed  Google Scholar 

  19. Schneider M, Zimmermann AG, Roberts RA, Zhang L, Swanson KV, Wen H, Davis BK, Allen IC, Holl EK, Ye Z et al (2012) The innate immune sensor NLRC3 attenuates Toll-like receptor signaling via modification of the signaling adaptor TRAF6 and transcription factor NF-kappaB. Nat Immunol 13:823–831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Maruyama K, Kawagoe T, Kondo T, Akira S, Takeuchi O (2012) TRAF family member-associated NF-kappaB activator (TANK) is a negative regulator of osteoclastogenesis and bone formation. J Biol Chem 287:29114–29124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Zhou F, Zhang X, van Dam H, Ten Dijke P, Huang H, Zhang L (2012) Ubiquitin-specific protease 4 mitigates toll-like/interleukin-1 receptor signaling and regulates innate immune activation. J Biol Chem 287:11002–11010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Hamidi A, von Bulow V, Hamidi R, Winssinger N, Barluenga S, Heldin CH, Landstrom M (2012) Polyubiquitination of transforming growth factor beta (TGFbeta)-associated kinase 1 mediates nuclear factor-kappaB activation in response to different inflammatory stimuli. J Biol Chem 287:123–133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wang HJ, Ruan HJ, He XJ, Ma YY, Jiang XT, Xia YJ, Ye ZY, Tao HQ (2010) MicroRNA-101 is down-regulated in gastric cancer and involved in cell migration and invasion. Eur J Cancer 46:2295–2303

    Article  CAS  PubMed  Google Scholar 

  24. Jacobs W, Mikkelsen T, Smith R, Nelson K, Rosenblum ML, Kohn EC (1997) Inhibitory effects of CAI in glioblastoma growth and invasion. J Neurooncol 32:93–101

    Article  CAS  PubMed  Google Scholar 

  25. Meng QH, Zhou LX, Luo JL, Cao JP, Tong J, Fan SJ (2005) Effect of 7-hydroxystaurosporine on glioblastoma cell invasion and migration. Acta Pharmacol Sin 26:492–499

    Article  CAS  PubMed  Google Scholar 

  26. Walsh MC, Kim GK, Maurizio PL, Molnar EE, Choi Y (2008) TRAF6 autoubiquitination-independent activation of the NFkappaB and MAPK pathways in response to IL-1 and RANKL. PLoS One 3:e4064

    Article  PubMed  PubMed Central  Google Scholar 

  27. Inubushi T, Kawazoe A, Miyauchi M, Kudo Y, Ao M, Ishikado A, Makino T, Takata T (2012) Molecular mechanisms of the inhibitory effects of bovine lactoferrin on lipopolysaccharide-mediated osteoclastogenesis. J Biol Chem 287:23527–23536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Hartupee J, Li X, Hamilton T (2008) Interleukin 1alpha-induced NFkappaB activation and chemokine mRNA stabilization diverge at IRAK1. J Biol Chem 283:15689–15693

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Lim KH, Yang Y, Staudt LM (2012) Pathogenetic importance and therapeutic implications of NF-kappaB in lymphoid malignancies. Immunol Rev 246:359–378

    Article  PubMed  PubMed Central  Google Scholar 

  30. Baldwin AS (2012) Regulation of cell death and autophagy by IKK and NF-kappaB: critical mechanisms in immune function and cancer. Immunol Rev 246:327–345

    Article  PubMed  Google Scholar 

  31. Ling J, Kumar R (2012) Crosstalk between NF-kB and glucocorticoid signaling: a potential target of breast cancer therapy. Cancer Lett 322:119–126

    Article  CAS  PubMed  Google Scholar 

  32. Zhong L, Cao F, You Q (2012) Effect of TRAF6 on the biological behavior of human lung adenocarcinoma cell. Tumour Biol. doi:10.1007/s13277-012-0543-8

  33. Liu H, Zhang T, Ye J, Li H, Huang J, Li X, Wu B, Huang X, Hou J (2012) TNF receptor-associated factor 6 in advanced non-small cell lung cancer: clinical and prognostic implications. J Cancer Res Clin Oncol 138:1853–1863

    Article  CAS  PubMed  Google Scholar 

  34. Chaudhry SI, Hooper S, Nye E, Williamson P, Harrington K, Sahai E (2012) Autocrine IL-1beta-TRAF6 signalling promotes squamous cell carcinoma invasion through paracrine TNFalpha signalling to carcinoma-associated fibroblasts. Oncogene. doi: 10.1038/onc.2012.91

  35. Meng Q, Zheng M, Liu H, Song C, Zhang W, Yan J, Qin L, Liu X (2012) TRAF6 regulates proliferation, apoptosis, and invasion of osteosarcoma cell. Mol Cell Biochem 371:177–186

    Article  CAS  PubMed  Google Scholar 

  36. Li YF, Xu XB, Chen XH, Wei G, He B, Wang JD (2012) The nuclear factor-kappaB pathway is involved in matrix metalloproteinase-9 expression in RU486-induced endometrium breakdown in mice. Hum Reprod 27:2096–2106

    Article  CAS  PubMed  Google Scholar 

  37. Cock-Rada AM, Medjkane S, Janski N, Yousfi N, Perichon M, Chaussepied M, Chluba J, Langsley G, Weitzman JB (2012) SMYD3 promotes cancer invasion by epigenetic upregulation of the metalloproteinase MMP-9. Cancer Res 72:810–820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Yang L, Zeng W, Li D, Zhou R (2009) Inhibition of cell proliferation, migration and invasion by DNAzyme targeting MMP-9 in A549 cells. Oncol Rep 22:121–126

    Article  CAS  PubMed  Google Scholar 

  39. Jee BK, Park KM, Surendran S, Lee WK, Han CW, Kim YS, Lim Y (2006) KAI1/CD82 suppresses tumor invasion by MMP9 inactivation via TIMP1 up-regulation in the H1299 human lung carcinoma cell line. Biochem Biophys Res Commun 342:655–661

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, NO.88, Jian-kang Road, Xinxiang, 453100, Henan, China

    Zhang Peng & Yue Shuangzhu

  2. Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453100, China

    Jiang Yongjie & Liu Ying

  3. Department of Urology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453100, China

    Zhang Xinjun

Authors
  1. Zhang Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yue Shuangzhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jiang Yongjie
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhang Xinjun
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Liu Ying
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhang Peng.

Additional information

An erratum to this article is available at http://dx.doi.org/10.1007/s11010-016-2682-5.

The Editor-in-Chief retracts this article as per the Committee on Publication Ethics (COPE) guidelines on plagiarism. After a thorough investigation, it was found that there is a striking level of similarity in the layout and content of this paper with another publication (Tumor Biology (2013) 34:231-239; doi:10.1007/s13277-012-0543-8). It is also pointed out that the authors have failed to the authors have failed to respond to these similarity issues, first brought to their attention in 2015.

About this article

Cite this article

Peng, Z., Shuangzhu, Y., Yongjie, J. et al. RETRACTED ARTICLE: TNF receptor-associated factor 6 regulates proliferation, apoptosis, and invasion of glioma cells. Mol Cell Biochem 377, 87–96 (2013). https://doi.org/10.1007/s11010-013-1573-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-013-1573-2

Keywords

Search

Navigation