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Article

Calcium/calmodulin‑dependent protein kinase II enhances metastasis of human gastric cancer by upregulating nuclear factor‑κB and Akt‑mediated matrix metalloproteinase‑9 production

  • Authors:
    • Zhaolong Liu
    • Gang Han
    • Yu Cao
    • Yidong Wang
    • Hangjun Gong
  • View Affiliations / Copyright

    Affiliations: Department of General Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China
  • Pages: 2459-2464
    |
    Published online on: August 28, 2014
       https://doi.org/10.3892/mmr.2014.2525
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Abstract

Calcium/calmodulin‑dependent protein kinase II (CaMKII) is a multi-functional serine/threonine protein kinase, involved in processes that cause tumor progression, including cell cycle regulation, apoptosis and differentiation. However, the role of CaMKII in cancer cell metastasis has not been fully elucidated. In the present study, the function of CaMKII in gastric cancer cell metastasis is reported. Firstly, it was demonstrated that the overexpression of H282R (constitutively active CaMKII) enhanced gastric cancer cell migration and invasion, and the inhibition of CaMKII activity by KN‑62 decreased gastric cancer cell metastasis. Furthermore, H282R upregulated matrix metalloproteinase‑9 (MMP‑9) expression and production, which were dependent on CaMKII‑mediated increase in nuclear factor (NF)‑κB and Akt activation. Finally, CaMKII activation, through phosphorylation of the Thr 286 site, was significantly increased in the metastatic gastric cancer tissues compared with non‑metastatic tissues, suggesting that CaMKII has an important function in the regulation of gastric cancer cell metastasis. Collectively, the present study demonstrated that CaMKII promotes gastric cancer cell metastasis by NF‑κB and Akt‑mediated‑MMP‑9 production. These findings suggest a novel function of CaMKII in the control of gastric cancer metastasis, offering a promising target for future therapeutics to treat and prevent gastric cancer metastases via the inhibition of CaMKII activity.
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Copy and paste a formatted citation
Spandidos Publications style
Liu Z, Han G, Cao Y, Wang Y and Gong H: Calcium/calmodulin‑dependent protein kinase II enhances metastasis of human gastric cancer by upregulating nuclear factor‑κB and Akt‑mediated matrix metalloproteinase‑9 production. Mol Med Rep 10: 2459-2464, 2014.
APA
Liu, Z., Han, G., Cao, Y., Wang, Y., & Gong, H. (2014). Calcium/calmodulin‑dependent protein kinase II enhances metastasis of human gastric cancer by upregulating nuclear factor‑κB and Akt‑mediated matrix metalloproteinase‑9 production. Molecular Medicine Reports, 10, 2459-2464. https://doi.org/10.3892/mmr.2014.2525
MLA
Liu, Z., Han, G., Cao, Y., Wang, Y., Gong, H."Calcium/calmodulin‑dependent protein kinase II enhances metastasis of human gastric cancer by upregulating nuclear factor‑κB and Akt‑mediated matrix metalloproteinase‑9 production". Molecular Medicine Reports 10.5 (2014): 2459-2464.
Chicago
Liu, Z., Han, G., Cao, Y., Wang, Y., Gong, H."Calcium/calmodulin‑dependent protein kinase II enhances metastasis of human gastric cancer by upregulating nuclear factor‑κB and Akt‑mediated matrix metalloproteinase‑9 production". Molecular Medicine Reports 10, no. 5 (2014): 2459-2464. https://doi.org/10.3892/mmr.2014.2525
Copy and paste a formatted citation
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Spandidos Publications style
Liu Z, Han G, Cao Y, Wang Y and Gong H: Calcium/calmodulin‑dependent protein kinase II enhances metastasis of human gastric cancer by upregulating nuclear factor‑κB and Akt‑mediated matrix metalloproteinase‑9 production. Mol Med Rep 10: 2459-2464, 2014.
APA
Liu, Z., Han, G., Cao, Y., Wang, Y., & Gong, H. (2014). Calcium/calmodulin‑dependent protein kinase II enhances metastasis of human gastric cancer by upregulating nuclear factor‑κB and Akt‑mediated matrix metalloproteinase‑9 production. Molecular Medicine Reports, 10, 2459-2464. https://doi.org/10.3892/mmr.2014.2525
MLA
Liu, Z., Han, G., Cao, Y., Wang, Y., Gong, H."Calcium/calmodulin‑dependent protein kinase II enhances metastasis of human gastric cancer by upregulating nuclear factor‑κB and Akt‑mediated matrix metalloproteinase‑9 production". Molecular Medicine Reports 10.5 (2014): 2459-2464.
Chicago
Liu, Z., Han, G., Cao, Y., Wang, Y., Gong, H."Calcium/calmodulin‑dependent protein kinase II enhances metastasis of human gastric cancer by upregulating nuclear factor‑κB and Akt‑mediated matrix metalloproteinase‑9 production". Molecular Medicine Reports 10, no. 5 (2014): 2459-2464. https://doi.org/10.3892/mmr.2014.2525
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