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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 is an international journal devoted to molecular mechanisms of human disease.

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

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Article

Osteopontin promotes the progression of gastric cancer through the NF-κB pathway regulated by the MAPK and PI3K

  • Authors:
    • Jie Liu
    • Qishen Liu
    • Yali Wan
    • Zhigang Zhao
    • Honggang Yu
    • Hesheng Luo
    • Zhongzhi Tang
  • View Affiliations / Copyright

    Affiliations: Department of Emergency Intensive Care Unit, Wuhan General Hospital of Guangzhou Command, Hubei, P.R. China , Department of Gastroenterology, Xianning Hospital, Hubei, P.R. China, Department of Gastroenterology, Renmin Hospital of Wuhan University, Hubei, P.R. China
  • Pages: 282-290
    |
    Published online on: April 17, 2014
       https://doi.org/10.3892/ijo.2014.2393
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Abstract

To elucidate the biological functions of osteopontin (OPN) in gastric tumors and to better understand the molecular events of OPN responsible for the malignancy, the present studies were performed. Growth curve, apoptosis assay, invasion assay and migration assay revealed that OPN status significantly affected proliferation, apoptosis, invasion and migration in gastric cancer cell lines. In mouse xenograft models of human gastric cancer, OPN silencing significantly inhibited tumor growth and the incidence of metastasis compared with non-silenced control. Mechanistic investigations revealed that OPN silencing inhibited the mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K) and phosphoinositide 3-kinase (NF-κB) pathways, and OPN-mediated NF-κB activity was reduced in the presence of MAPK or PI3K inhibitor. Our findings also indicated that OPN through the NF-κB pathway promotes the expression of matrix metalloproteinase 2 (MMP-2), MMP-9 and urokinase-type plasminogen activator (uPA), the activation of MMP-2 and MMP-9, and the inhibition of caspase-3. Taken together, our results reveal that OPN promotes the progression of gastric cancer through the NF-κB pathway, which is regulated by the MAPK and PI3K pathways and leads to MMP-2, MMP-9 and uPA activation and caspase-3 inhibition. These findings identify OPN as a novel oncogene in gastric cancer and suggest that OPN is an attractive therapeutic target for this aggressive malignancy.
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Copy and paste a formatted citation
Spandidos Publications style
Liu J, Liu Q, Wan Y, Zhao Z, Yu H, Luo H and Tang Z: Osteopontin promotes the progression of gastric cancer through the NF-κB pathway regulated by the MAPK and PI3K. Int J Oncol 45: 282-290, 2014.
APA
Liu, J., Liu, Q., Wan, Y., Zhao, Z., Yu, H., Luo, H., & Tang, Z. (2014). Osteopontin promotes the progression of gastric cancer through the NF-κB pathway regulated by the MAPK and PI3K. International Journal of Oncology, 45, 282-290. https://doi.org/10.3892/ijo.2014.2393
MLA
Liu, J., Liu, Q., Wan, Y., Zhao, Z., Yu, H., Luo, H., Tang, Z."Osteopontin promotes the progression of gastric cancer through the NF-κB pathway regulated by the MAPK and PI3K". International Journal of Oncology 45.1 (2014): 282-290.
Chicago
Liu, J., Liu, Q., Wan, Y., Zhao, Z., Yu, H., Luo, H., Tang, Z."Osteopontin promotes the progression of gastric cancer through the NF-κB pathway regulated by the MAPK and PI3K". International Journal of Oncology 45, no. 1 (2014): 282-290. https://doi.org/10.3892/ijo.2014.2393
Copy and paste a formatted citation
x
Spandidos Publications style
Liu J, Liu Q, Wan Y, Zhao Z, Yu H, Luo H and Tang Z: Osteopontin promotes the progression of gastric cancer through the NF-κB pathway regulated by the MAPK and PI3K. Int J Oncol 45: 282-290, 2014.
APA
Liu, J., Liu, Q., Wan, Y., Zhao, Z., Yu, H., Luo, H., & Tang, Z. (2014). Osteopontin promotes the progression of gastric cancer through the NF-κB pathway regulated by the MAPK and PI3K. International Journal of Oncology, 45, 282-290. https://doi.org/10.3892/ijo.2014.2393
MLA
Liu, J., Liu, Q., Wan, Y., Zhao, Z., Yu, H., Luo, H., Tang, Z."Osteopontin promotes the progression of gastric cancer through the NF-κB pathway regulated by the MAPK and PI3K". International Journal of Oncology 45.1 (2014): 282-290.
Chicago
Liu, J., Liu, Q., Wan, Y., Zhao, Z., Yu, H., Luo, H., Tang, Z."Osteopontin promotes the progression of gastric cancer through the NF-κB pathway regulated by the MAPK and PI3K". International Journal of Oncology 45, no. 1 (2014): 282-290. https://doi.org/10.3892/ijo.2014.2393
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