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International Journal of Oncology
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Print ISSN: 1019-6439 Online ISSN: 1791-2423
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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.

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International Journal of Oncology

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

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

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

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

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

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Molecular and Clinical Oncology

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

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International Journal of Functional Nutrition

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Article

TIPE2 functions as a metastasis suppressor via negatively regulating β-catenin through activating GSK3β in gastric cancer

  • Authors:
    • Jie Wu
    • Haitao Zhang
    • Chun Xu
    • Hong Xu
    • Xiumin Zhou
    • Yufeng Xie
    • Min Tao
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China, Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China
  • Pages: 199-206
    |
    Published online on: October 30, 2015
       https://doi.org/10.3892/ijo.2015.3224
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Abstract

Tumor necrosis factor (TNF)-α-induced protein 8-like 2 (TNFAIP8L2, TIPE2) is a novel anti-inflammatory factor involved in maintaining immune homeostasis. Accumulating evidence has also shown that TIPE2 displays tumor-suppressive effects in several tumor types. Previous studies revealed that TIPE2 inhibits hepatocellular carcinoma metastasis by repressing Ral and Rac1 GTPases. However, its antimetastatic activity and underlying mechanism in other human cancers is largely unknown. We investigated TIPE2 in AGS, HGC-27 and SGC-7901 human gastric cancer cells compared with GES-1 normal human gastric mucous epithelial cells. We demonstrated that TIPE2 was expressed in GES-1 gastric mucous epithelial cells but lost in all three types of gastric cancer cells. We then performed a gain-of-function study by adenovirus-mediated TIPE2 overexpression (AdVTIPE2) and investigated the effects of TIPE2 on migration and invasion of AGS human gastric cancer cells. Wound healing and Transwell invasion assays showed that forced expression of TIPE2 markedly suppressed the gastric cancer cell migration and invasion in vitro. Mechanistically, TIPE2 remarkably reduced the total levels of pAKT, pGSK3β and β-catenin as well as the nuclear level of β-catenin in gastric cancer cells. The TIPE2-elicited antimetastatic effect in gastric cancer was closely associated with the inhibition of AKT signaling and enhancement of GSK3β activity followed by the degradation and decreased translocation to nucleus of β-catenin. These results provide the first compelling evidence that TIPE2 suppresses gastric cancer metastasis via downregulating β-catenin signaling through inhibiting AKT and activating GSK3β, indicating that TIPE2 is a promising therapeutic target for human gastric cancer metastasis.
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Copy and paste a formatted citation
Spandidos Publications style
Wu J, Zhang H, Xu C, Xu H, Zhou X, Xie Y and Tao M: TIPE2 functions as a metastasis suppressor via negatively regulating β-catenin through activating GSK3β in gastric cancer. Int J Oncol 48: 199-206, 2016.
APA
Wu, J., Zhang, H., Xu, C., Xu, H., Zhou, X., Xie, Y., & Tao, M. (2016). TIPE2 functions as a metastasis suppressor via negatively regulating β-catenin through activating GSK3β in gastric cancer. International Journal of Oncology, 48, 199-206. https://doi.org/10.3892/ijo.2015.3224
MLA
Wu, J., Zhang, H., Xu, C., Xu, H., Zhou, X., Xie, Y., Tao, M."TIPE2 functions as a metastasis suppressor via negatively regulating β-catenin through activating GSK3β in gastric cancer". International Journal of Oncology 48.1 (2016): 199-206.
Chicago
Wu, J., Zhang, H., Xu, C., Xu, H., Zhou, X., Xie, Y., Tao, M."TIPE2 functions as a metastasis suppressor via negatively regulating β-catenin through activating GSK3β in gastric cancer". International Journal of Oncology 48, no. 1 (2016): 199-206. https://doi.org/10.3892/ijo.2015.3224
Copy and paste a formatted citation
x
Spandidos Publications style
Wu J, Zhang H, Xu C, Xu H, Zhou X, Xie Y and Tao M: TIPE2 functions as a metastasis suppressor via negatively regulating β-catenin through activating GSK3β in gastric cancer. Int J Oncol 48: 199-206, 2016.
APA
Wu, J., Zhang, H., Xu, C., Xu, H., Zhou, X., Xie, Y., & Tao, M. (2016). TIPE2 functions as a metastasis suppressor via negatively regulating β-catenin through activating GSK3β in gastric cancer. International Journal of Oncology, 48, 199-206. https://doi.org/10.3892/ijo.2015.3224
MLA
Wu, J., Zhang, H., Xu, C., Xu, H., Zhou, X., Xie, Y., Tao, M."TIPE2 functions as a metastasis suppressor via negatively regulating β-catenin through activating GSK3β in gastric cancer". International Journal of Oncology 48.1 (2016): 199-206.
Chicago
Wu, J., Zhang, H., Xu, C., Xu, H., Zhou, X., Xie, Y., Tao, M."TIPE2 functions as a metastasis suppressor via negatively regulating β-catenin through activating GSK3β in gastric cancer". International Journal of Oncology 48, no. 1 (2016): 199-206. https://doi.org/10.3892/ijo.2015.3224
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