Skip to main content

Advertisement

SpringerLink
Log in

Ubiquitin-Conjugating Enzyme E2T is an Independent Prognostic Factor and Promotes Gastric Cancer Progression

  • Original Article
  • Published:
Tumor Biology

Abstract

Ubiquitin-conjugating enzyme E2T (UBE2T) is a member of the E2 family that mediates the ubiquitin-proteasome system and regulates gene expression. It is a major oncogene in several cancers such as lung cancer and breast cancer, while the potential functions of UBE2T in gastric cancer (GC) remains largely unknown. Here, we identified the roles of UBE2T in GC progression and its potential to act as a prognostic marker of GC. Our data demonstrated that UBE2T was significantly upregulated in gastric cancer tissues, and the high expression of UBE2T was significantly correlated with poor differentiation, high T classification, and poor prognosis. In vitro experiments indicated that UBE2T promoted cell proliferation and inhibited cell cycle arrest. In addition, we observed that UBE2T modulated cell mobility by inducing epithelial-mesenchymal transition. Collectively, these findings suggest that UBE2T plays an important role in the tumorigenesis of gastric cancer and could act as a potential independent prognostic factor for cancer therapy.

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

We’re sorry, something doesn't seem to be working properly.

Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

References

  1. Ang TL, Fock KM. Clinical epidemiology of gastric cancer. Singap Med J. 2014;55:621–8.

    Article  Google Scholar 

  2. Zilberstein B et al. Gastric cancer trends in epidemiology. Arq Gastroenterol. 2012;49:177–8.

    Article  PubMed  Google Scholar 

  3. Karimi P et al. Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol. 2014;23:700–13.

    Article  Google Scholar 

  4. Kanda M, Kodera Y. Recent advances in the molecular diagnostics of gastric cancer. World J Gastroenterol WJG. 2015;21:9838–52.

    Article  CAS  PubMed  Google Scholar 

  5. Zhang WH et al. Outcomes of surgical treatment for gastric cancer patients: 11-year experience of a Chinese high-volume hospital. Med Oncol. 2014;31:150.

    Article  PubMed  Google Scholar 

  6. Zhai R et al (2014) miR-152 suppresses gastric cancer cell proliferation and motility by targeting CD151. Tumour Biol J Int Soc Oncodev Biol Med

  7. Machida YJ et al. UBE2T is the E2 in the Fanconi anemia pathway and undergoes negative autoregulation. Mol Cell. 2006;23:589–96.

    Article  CAS  PubMed  Google Scholar 

  8. Alpi A et al. UBE2T, the Fanconi anemia core complex, and FANCD2 are recruited independently to chromatin: a basis for the regulation of FANCD2 monoubiquitination. Mol Cell Biol. 2007;27:8421–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Corson TW et al. KIF14 is a candidate oncogene in the 1q minimal region of genomic gain in multiple cancers. Oncogene. 2005;24:4741–53.

    Article  CAS  PubMed  Google Scholar 

  10. Hao J et al. Elevated expression of UBE2T in lung cancer tumors and cell lines. Tumour Biol J Int Soc Oncodev Biol Med. 2008;29:195–203.

    Article  CAS  Google Scholar 

  11. Kikuchi T et al. Expression profiles of non-small cell lung cancers on cDNA microarrays: identification of genes for prediction of lymph-node metastasis and sensitivity to anti-cancer drugs. Oncogene. 2003;22:2192–205.

    Article  CAS  PubMed  Google Scholar 

  12. Takata R et al. Predicting response to methotrexate, vinblastine, doxorubicin, and cisplatin neoadjuvant chemotherapy for bladder cancers through genome-wide gene expression profiling. Clin Cancer Res Off J Am Assoc Cancer Res. 2005;11:2625–36.

    Article  CAS  Google Scholar 

  13. Wen M et al. Elevated expression of UBE2T exhibits oncogenic properties in human prostate cancer. Oncotarget. 2015;6:25226–39.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Zhai J et al. miR-129 suppresses tumor cell growth and invasion by targeting PAK5 in hepatocellular carcinoma. Biochem Biophys Res Commun. 2015;464:161–7.

    Article  CAS  PubMed  Google Scholar 

  15. Lin Y et al. Gene mutations in gastric cancer: a review of recent next-generation sequencing studies. Tumour Biol J Int Soc Oncodev Biol Med. 2015;36:7385–94.

    Article  CAS  Google Scholar 

  16. Tsunoda S et al (2014) Laparoscopic gastrectomy for remnant gastric cancer: a comprehensive review and case series. Gastric Cancer Off J Int Gastric Cancer Assoc Jpn Gastric Cancer Assoc

  17. Takahashi Y et al. The usefulness of CEA and/or CA19-9 in monitoring for recurrence in gastric cancer patients: a prospective clinical study. Gastric Cancer Off J Int Gastric Cancer Assoc Jpn Gastric Cancer Assoc. 2003;6:142–5.

    Google Scholar 

  18. Kochi M et al. Evaluation of serum CEA and CA19-9 levels as prognostic factors in patients with gastric cancer. Gastric Cancer Off J Int Gastric Cancer Assoc Jpn Gastric Cancer Assoc. 2000;3:177–86.

    Google Scholar 

  19. Hira A et al. Mutations in the gene encoding the E2 conjugating enzyme UBE2T cause Fanconi anemia. Am J Hum Genet. 2015;96:1001–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Rickman KA et al. Deficiency of UBE2T, the E2 ubiquitin ligase necessary for FANCD2 and FANCI ubiquitination, causes FA-T subtype of Fanconi anemia. Cell Rep. 2015;12:35–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Virts EL et al. AluY-mediated germline deletion, duplication and somatic stem cell reversion in UBE2T defines a new subtype of Fanconi anemia. Hum Mol Genet. 2015;24:5093–108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ramaekers CH et al. Hypoxia disrupts the Fanconi anemia pathway and sensitizes cells to chemotherapy through regulation of UBE2T. Radiother Oncol J Eur Soc Ther Radiol Oncol. 2011;101:190–7.

    Article  CAS  Google Scholar 

  23. Kelsall IR et al. The Fanconi anaemia components UBE2T and FANCM are functionally linked to nucleotide excision repair. PLoS One. 2012;7, e36970.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ueki T et al. Ubiquitination and downregulation of BRCA1 by ubiquitin-conjugating enzyme E2T overexpression in human breast cancer cells. Cancer Res. 2009;69:8752–60.

    Article  CAS  PubMed  Google Scholar 

  25. Huang N et al. MiR-338-3p inhibits epithelial-mesenchymal transition in gastric cancer cells by targeting ZEB2 and MACC1/Met/Akt signaling. Oncotarget. 2015;6:15222–34.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Yoo YA et al. Sonic hedgehog pathway promotes metastasis and lymphangiogenesis via activation of Akt, EMT, and MMP-9 pathway in gastric cancer. Cancer Res. 2011;71:7061–70.

    Article  CAS  PubMed  Google Scholar 

  27. Yang Y et al. C23 protein meditates bone morphogenetic protein-2-mediated EMT via up-regulation of Erk1/2 and Akt in gastric cancer. Med Oncol. 2015;32:76.

    Article  PubMed  Google Scholar 

  28. Bullock MD et al. MicroRNAs: critical regulators of epithelial to mesenchymal (EMT) and mesenchymal to epithelial transition (MET) in cancer progression. Biol Cell Under Auspices Eur Cell Biol Organ. 2012;104:3–12.

    Article  CAS  Google Scholar 

  29. De Craene B, Berx G. Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer. 2013;13:97–110.

    Article  PubMed  Google Scholar 

  30. Iwanaga R et al. Expression of Six1 in luminal breast cancers predicts poor prognosis and promotes increases in tumor initiating cells by activation of extracellular signal-regulated kinase and transforming growth factor-beta signaling pathways. Breast Cancer Res BCR. 2012;14:R100.

    Article  CAS  PubMed  Google Scholar 

  31. Che J et al. Decreased expression of claudin-3 is associated with a poor prognosis and EMT in completely resected squamous cell lung carcinoma. Tumour Biol J Int Soc Oncodev Biol Med. 2015;36:6559–68.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Oncology, Binhu Traditional Chinese Medicine Hospital, 390#, Xinchengdao Road, Binhu District, Wuxi, Jiangsu Province, 214121, People’s Republic of China

    Hao Yu, Pei Xiang, Qi Pan, Yijiao Huang, Nanlan Xie & Weimin Zhu

Authors
  1. Hao Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pei Xiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qi Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yijiao Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nanlan Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Weimin Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Weimin Zhu.

Ethics declarations

This study was supported by the Ethics Committee of Binhu Traditional Chinese Medicine Hospital. All patients agreed to participate in the study and gave written informed consent. The tissue microarray (TMA) containing 180 cases of gastric cancer specimens used in this study was purchased from Shanghai Outdo Biotech Inc, and the clinicopathological features were complete.

Conflicts of Interest

None

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

Supplementary Table S1

(DOCX 14 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yu, H., Xiang, P., Pan, Q. et al. Ubiquitin-Conjugating Enzyme E2T is an Independent Prognostic Factor and Promotes Gastric Cancer Progression. Tumor Biol. 37, 11723–11732 (2016). https://doi.org/10.1007/s13277-016-5020-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-016-5020-3

Keywords

Search

Navigation