Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
September-2018 Volume 40 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
September-2018 Volume 40 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

TIPE2 inhibits GC via regulation of cell proliferation, apoptosis and inflammation

  • Authors:
    • Zhenhe Lin
    • Wenming Liu
    • Chuanxing Xiao
    • Yanyun Fan
    • Guohong Zhuang
    • Zhongquan Qi
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian 361004, P.R. China, Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian 361004, P.R. China, Organ Transplantation Institute, Anti‑Cancer Research Center, Medical College of Xiamen University, Xiamen, Fujian 361102, P.R. China
    Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1307-1316
    |
    Published online on: July 13, 2018
       https://doi.org/10.3892/or.2018.6576
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Gastric cancer (GC), a type of gastric mucosal epithelium disease caused by common malignant tumors, has become a major threat to human health and survival. Tumor necrosis factor‑α‑induced protein‑8 like‑2 (TIPE2) is a negative immune regulatory factor that is selectively expressed in immune organs, immune cells and various epithelial cells and serves an important role in the maintenance of human physiological immune homeostasis. In our preliminary study, we found that the expression of TIPE2 was downregulated or absent in GC tissues compared with normal gastric mucosa tissues, indicating that TIPE2 may play a significant role in the development of GC. To clarify the role of TIPE2 in the progression of human GC and to elucidate the underlying mechanism, the association between TIPE2 and phosphatidylinositol 3‑kinase (PI3K)/AKT, the cell cycle, the caspase‑related apoptosis pathway and the NF‑κB signaling pathway were investigated through western blot and flow cytometric analysis. It was determined that TIPE2 inhibited GC cell proliferation mainly by reducing the expression of phosphorylated AKT and ERK, which caused subsequent inhibition of the PI3K‑AKT and Ras‑Raf‑MEK‑ERK1/2 signaling pathways. Additionally, we investigated the relationship between TIPE2 and GC and discovered that TIPE2 inhibited tumor progression via growth, apoptosis and inflammatory pathways. The results of the present study provided a theoretical basis for the development and application of TIPE2 as an antitumor agent.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

View References

1 

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

2 

Fang JY, Cheng ZH, Chen YX, Lu R, Yang L, Zhu HY and Lu LG: Expression of Dnmt1, demethylase, MeCP2 and methylation of tumor-related genes in human GC. World J Gastroenterol. 10:3394–3398. 2004. View Article : Google Scholar : PubMed/NCBI

3 

Chen CN, Lin JJ, Chen JJ, Lee PH, Yang CY, Kuo ML, Chang KJ and Hsieh FJ: Gene expression profile predicts patient survival of GC after surgical resection. J Am Soc Clin Oncol. 23:7286–7295. 2005. View Article : Google Scholar

4 

Nathan C and Ding A: Nonresolving inflammation. Cell. 140:871–882. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Sun HH, Gong S, Carmody RJ, Hilliard A, Li L, Sun J, Kong L, Xu L, Hilliard B, Hu S, et al: TIPE2, a negative regulator of innate and adaptive immunity that maintains immune homeostasis. Cell. 133:415–426. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Wang K, Ren Y, Liu Y, Zhang J and He JJ: Tumor necrosis factor (TNF)-alpha-induced protein 8-like-2 (TIPE2) inhibits proliferation and tumorigenesis in breast cancer cells. Oncol Res. 25:55–63. 2017. View Article : Google Scholar : PubMed/NCBI

7 

Zhang X, Wang J, Fan C, Li H, Sun H, Gong S, Chen YH and Shi Y: Crystal structure of TIPE2 provides insights into immune homeostasis. Nat Struct Mol Biol. 16:89–90. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Xi W, Hu Y, Liu Y, Zhang J, Wang L, Lou Y, Qu Z, Cui J, Zhang G, Liang X, et al: Roles of TIPE2 in hepatitis B virus-induced hepatic inflammation in humans and mice. Mol Immunol. 48:1203–1208. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Zhang L, Shi Y, Wang Y, Zhu F, Wang Q, Ma C, Chen YH and Zhang L: The unique expression profile of human TIPE2 suggests new functions beyond its role in immune regulation. Mol Immunol. 48:1209–1215. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Fayngerts SA, Wang ZJ, Zamani A, Sun H, Boggs AE, Porturas TP, Xie W, Lin M, Cathopoulis T, Goldsmith JR, et al: Direction of leukocyte polarization and migration by the phosphoinositide-transfer protein TIPE2. Nat Immunol. 18:1353–1360. 2017. View Article : Google Scholar : PubMed/NCBI

11 

Sun H, Zhuang G, Chai L, Wang Z, Johnson D, Ma Y and Chen YH: TIPE2 controls innate immunity to RNA by targeting the phosphatidylinositol 3-kinase-Rac pathway. J Immunol. 189:2768–2773. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Zhu Y, Tao M, Wu J, Meng Y, Xu C, Tian Y, Zhou X, Xiang J, Zhang H and Xie Y: Adenovirus-directed expression of TIPE2 suppresses GC growth via induction of apoptosis and inhibition of AKT and ERK1/2 signaling. Cancer Gene Ther. 23:98–106. 2016. View Article : Google Scholar : PubMed/NCBI

13 

Zhao Q, Zhao M, Dong T, Zhou C, Peng Y, Zhou X, Fan B, Ma W, Han M and Liu S: Tumor necrosis factor-α-induced protein-8 like-2 (TIPE2) upregulates p27 to decrease gastic cancer cell proliferation. J Cell Biochem. 116:1121–1129. 2015. View Article : Google Scholar : PubMed/NCBI

14 

Cao XL, Zhang L, Shi YY, Sun Y, Dai S, Guo C, Zhu F, Wang Q, Wang J, Wang X, et al: Human tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 suppresses hepatocellular carcinoma metastasis through inhibiting Rac1. Mol Cancer. 12:1492013. View Article : Google Scholar : PubMed/NCBI

15 

Li XM, Su JR, Yan SP, Cheng ZL, Yang TT and Zhu Q: A novel inflammatory regulator TIPE2 inhibits TLR4-mediated development of colon cancer via caspase-8. Cancer Biomarkers. 14:233–240. 2014. View Article : Google Scholar : PubMed/NCBI

16 

Ruan H, Zhan YY, Hou J, Xu B, Chen B, Tian Y, Wu D, Zhao Y, Zhang Y, Chen X, et al: Berberine binds RXRα to suppress β-catenin signaling in colon cancer cells. Oncogene. 36:6906–6918. 2017. View Article : Google Scholar : PubMed/NCBI

17 

He K, Chen D, Ruan H, Li X, Tong J, Xu X, Zhang L and Yu J: BRAFV600E-dependent Mcl-1 stabilization leads to everolimus resistance in colon cancer cells. Oncotarget. 7:47699–47710. 2016.PubMed/NCBI

18 

Yao Y, Wang ZC, Liu JX, Ma J, Chen CL, Deng YK, Liao B, Wang N, Wang H, Ning Q, et al: Increased expression of TIPE2 in alternatively activated macrophages is associated with eosinophilic inflammation and disease severity in chronic rhinosinusitis with nasal polyps. Int Forum Allergy Rhinol. 7:963–972. 2017. View Article : Google Scholar : PubMed/NCBI

19 

Sun Y, Wang X, Li Y, Sun H, Wan L, Wang X, Zhang L, Fang Z and Wei Z: The decreased expression of TIPE2 protein in the decidua of patients with missed abortion and possible significance. Reprod Biol Endocrinol. 15:682017. View Article : Google Scholar : PubMed/NCBI

20 

Li X, Zhang Y, Li F, Zhu X and Huang L: Negative immune regulatory molecule tipe2 for treating sle mice through regulating macrophage subtype. Chongqing Med. 2017.

21 

Zhang Y, Mei S, Zhou Y, Yang D, Pan T, Chen Z and Wang Q: TIPE2 negatively regulates mycoplasma pneumonia-triggered immune response via MAPK signaling pathway. Sci Rep. 7:133192017. View Article : Google Scholar : PubMed/NCBI

22 

Liu RL, Fan TT, Geng WW, Chen YHH, Ruan QG and Zhang C: Negative immune regulator TIPE2 promotes M2 macrophage differentiation through the activation of PI3K-AKT signaling pathway. PLoS One. 12:e01706662017. View Article : Google Scholar : PubMed/NCBI

23 

Shi-Bai Z, Rui-Min L, Ying-Chuan S, Jie Z, Chao J, Can-Hua Y, Xi C and Wen-Wei Q: TIPE2 expression is increased in peripheral blood mononuclear cells from patients with rheumatoid arthritis. Oncotarget. 8:87472–87479. 2017. View Article : Google Scholar : PubMed/NCBI

24 

Jiang JS, Wang SS, Fang J, Xu Y, Tong L, Ye X and Zhou W: Stable silencing of TIPE2 reduced the Poly I:C-induced apoptosis in THP-1 cells. Mol Med Rep. 16:6313–6319. 2017. View Article : Google Scholar : PubMed/NCBI

25 

Zhang Z, Liu L, Cao S, Zhu Y and Mei Q: Gene delivery of TIPE2 inhibits breast cancer development and metastasis via CD8+ T and NK cell-mediated antitumor responses. Mol Immunol. 85:230–237. 2017. View Article : Google Scholar : PubMed/NCBI

26 

Zhang G, Zhang W, Lou Y, Xi W, Cui J, Geng M, Zhu F, Chen YH and Liu S: TIPE2 deficiency accelerates neointima formation by downregulating smooth muscle cell differentiation. Cell Cycle. 12:501–510. 2013. View Article : Google Scholar : PubMed/NCBI

27 

Kong L, Liu K, Zhang YZ, Jin M, Wu BR, Wang WZ, Li W, Nan YM and Chen YH: Downregulation of TIPE2 mRNA expression in peripheral blood mononuclear cells from patients with chronic hepatitis C. Hepato Int. 7:844–849. 2013. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Lin Z, Liu W, Xiao C, Fan Y, Zhuang G and Qi Z: TIPE2 inhibits GC via regulation of cell proliferation, apoptosis and inflammation. Oncol Rep 40: 1307-1316, 2018.
APA
Lin, Z., Liu, W., Xiao, C., Fan, Y., Zhuang, G., & Qi, Z. (2018). TIPE2 inhibits GC via regulation of cell proliferation, apoptosis and inflammation. Oncology Reports, 40, 1307-1316. https://doi.org/10.3892/or.2018.6576
MLA
Lin, Z., Liu, W., Xiao, C., Fan, Y., Zhuang, G., Qi, Z."TIPE2 inhibits GC via regulation of cell proliferation, apoptosis and inflammation". Oncology Reports 40.3 (2018): 1307-1316.
Chicago
Lin, Z., Liu, W., Xiao, C., Fan, Y., Zhuang, G., Qi, Z."TIPE2 inhibits GC via regulation of cell proliferation, apoptosis and inflammation". Oncology Reports 40, no. 3 (2018): 1307-1316. https://doi.org/10.3892/or.2018.6576
Copy and paste a formatted citation
x
Spandidos Publications style
Lin Z, Liu W, Xiao C, Fan Y, Zhuang G and Qi Z: TIPE2 inhibits GC via regulation of cell proliferation, apoptosis and inflammation. Oncol Rep 40: 1307-1316, 2018.
APA
Lin, Z., Liu, W., Xiao, C., Fan, Y., Zhuang, G., & Qi, Z. (2018). TIPE2 inhibits GC via regulation of cell proliferation, apoptosis and inflammation. Oncology Reports, 40, 1307-1316. https://doi.org/10.3892/or.2018.6576
MLA
Lin, Z., Liu, W., Xiao, C., Fan, Y., Zhuang, G., Qi, Z."TIPE2 inhibits GC via regulation of cell proliferation, apoptosis and inflammation". Oncology Reports 40.3 (2018): 1307-1316.
Chicago
Lin, Z., Liu, W., Xiao, C., Fan, Y., Zhuang, G., Qi, Z."TIPE2 inhibits GC via regulation of cell proliferation, apoptosis and inflammation". Oncology Reports 40, no. 3 (2018): 1307-1316. https://doi.org/10.3892/or.2018.6576
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team