Skip to main content

Advertisement

SpringerLink
Log in

TNFAIP8 Overexpression: Clinical Relevance to Esophageal Squamous Cell Carcinoma

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Tumor necrosis factor alpha-induced protein 8 (TNFAIP8) is a suppressor of TNF-α mediated apoptosis, and its expression is induced by NF-κB activation. TNFAIP8 expression is significantly increased in various cancer cell lines. A correlation between TNFAIP8 overexpression, cancer progression, and poor prognosis has been described in many reports of human solid cancers.

Methods

To clarify the functional and clinical significance of the cancer progression-related gene, TNFAIP8, in esophageal squamous cell carcinoma (ESCC), we used immunohistochemistry to demonstrate TNFAIP8 expression in ESCC. Next, TNFAIP8 expression was depleted by using siRNA to examine the function of TNFAIP8 in the proliferation and apoptosis induction of ESCC cell lines.

Results

We detected correlations between TNFAIP8 expression and TNM stage (P < 0.001), tumor depth (P = 0.002), lymph node metastasis (P = 0.013), distant metastasis (P = 0.001), lymphatic invasion (P < 0.001), and venous invasion (P < 0.001) among the clinicopathological characteristics of ESCC patients, and high TNFAIP8 expression was found in poor survival. TNFAIP8 depletion was significantly associated with apoptosis induction after cisplatin administration and reduced proliferation.

Conclusions

Our results suggest that TNFAIP8 might be an effective therapeutic target for ESCC in the future.

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

Similar content being viewed by others

References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.

    Article  PubMed  Google Scholar 

  2. Kato H, Fukuchi M, Miyazaki T, et al. Surgical treatment for esophageal cancer. Current issues. Dig Surg. 2007;24:88–95.

    Article  PubMed  Google Scholar 

  3. You Z, Ouyang H, Lopatin D, Polver PJ, Wang CY. Nuclear factor-kappa B-inducible death effector domain-containing protein suppresses tumor necrosis factor-mediated apoptosis by inhibiting caspase-8 activity. J Biol Chem. 2001;276:26398–404.

    Article  PubMed  CAS  Google Scholar 

  4. Zhang C, Chakravarty D, Sakabe I, et al. Role of SCC-S2 in experimental metastasis and modulation of VEGFR-2, MMP-1, and MMP-9 expression. Mol Ther. 2006;13:947–55.

    Article  PubMed  CAS  Google Scholar 

  5. Kumar D, Gokhale P, Broustas C, Chakravarty D, Ahmad I, Kasid U. Expression of SCC-S2, an antiapoptotic molecule, correlates with enhanced proliferation and tumorigenicity of MDA-MB 435 cells. Oncogene. 2004;23:612–6.

    Article  PubMed  CAS  Google Scholar 

  6. Zhang S, Zhang Y, Wei X, et al. Expression and regulation of a novel identified TNFAIP8 family is associated with diabetic nephropathy. Biochim Biophys Acta. 2010;1802:1078–86.

    Article  PubMed  CAS  Google Scholar 

  7. Kumar D, Whiteside TL, Kasid U. Identification of a novel tumor necrosis factor-alpha-inducible gene, SCC-S2, containing the consensus sequence of a death effector domain of fas-associated death domain-like interleukin- 1beta-converting enzyme-inhibitory protein. J Biol Chem. 2000;275:2973–8.

    Article  PubMed  CAS  Google Scholar 

  8. Zhang LJ, Liu X, Gafken PR, Kioussi C, Leid M. A chicken ovalbumin upstream promoter transcription factor I (COUP-TFI) complex represses expression of the gene encoding tumor necrosis factor alpha-induced protein 8 (TNFAIP8). J Biol Chem. 2009;284:6156–68.

    Article  PubMed  CAS  Google Scholar 

  9. Laliberte B, Wilson AM, Nafisi H, et al. TNFAIP8: a new effector for Galpha(i) coupling to reduce cell death and induce cell transformation. J Cell Physiol 2010;225:865–74.

    Article  PubMed  CAS  Google Scholar 

  10. Patel S, Wang FH, Whiteside TL, Kasid U. Identification of seven differentially displayed transcripts in human primary and matched metastatic head and neck squamous cell carcinoma cell lines: implications in metastasis and/or radiation response. Oral Oncol. 1997;33:197–203.

    Article  PubMed  CAS  Google Scholar 

  11. Dong QZ, Zhao Y, Liu Y, et al. Overexpression of SCC-S2 correlates with lymph node metastasis and poor prognosis in patients with non-small-cell lung cancer. Cancer Sci. 2010;101:1562–9.

    Article  PubMed  CAS  Google Scholar 

  12. Kirillova I, Chaisson M, Fausto N. Tumor necrosis factor induces DNA replication in hepatic cells through nuclear factor kappaB activation. Cell Growth Differ. 1999;10:819–28.

    PubMed  CAS  Google Scholar 

  13. Su WB, Chang YH, Lin WW, Hsieh SL. Differential regulation of interleukin-8 gene transcription by death receptor 3 (DR3) and type I TNF receptor (TNFRI). Exp Cell Res. 2006;312:266–77.

    PubMed  CAS  Google Scholar 

  14. Eisele L, Klein-Hitpass L, Chatzimanolis N, et al. Differential expression of drug-resistance-related genes between sensitive and resistant blasts in acute myeloid leukemia. Acta Haematol. 2007;117:8–15.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

We thank Ms. Masako Shin, Ms. Tomoko Yano, Ms. Sayaka Muraoka, Ms. Midori Ohno, Ms. Yuka Matsui, and Ms. Yukie Saito for their excellent assistance. This work was supported in part by the following grants and foundations: Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS); grant numbers 21591690, 22591450 and 23591857.

Author information

Authors and Affiliations

  1. Department of General Surgical Science (Surgery 1), Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan

    Yuni Elsa Hadisaputri Pharm.D, Tatsuya Miyazaki MD, PhD, Shigemasa Suzuki MD, Takehiko Yokobori MD, PhD, Tsutomu Kobayashi MD, PhD, Naritaka Tanaka MD, PhD, Takanori Inose MD, PhD, Makoto Sohda MD, PhD & Hiroyuki Kuwano MD, PhD

Authors
  1. Yuni Elsa Hadisaputri Pharm.D
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tatsuya Miyazaki MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shigemasa Suzuki MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Takehiko Yokobori MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tsutomu Kobayashi MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Naritaka Tanaka MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Takanori Inose MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Makoto Sohda MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hiroyuki Kuwano MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yuni Elsa Hadisaputri Pharm.D.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 263 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hadisaputri, Y.E., Miyazaki, T., Suzuki, S. et al. TNFAIP8 Overexpression: Clinical Relevance to Esophageal Squamous Cell Carcinoma. Ann Surg Oncol 19 (Suppl 3), 589–596 (2012). https://doi.org/10.1245/s10434-011-2097-1

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-011-2097-1

Keywords

Search

Navigation