title: Calcium/calmodulin‑dependent protein kinase II enhances metastasis of human gastric cancer by upregulating nuclear factor‑κB and Akt‑mediated matrix metalloproteinase‑9 production.
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.
authors.affiliation: Department of General Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China.
authors.forename: Zhaolong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Han
authors.affiliation: Department of General Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of General Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China.
authors.forename: Yidong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China.
authors.forename: Hangjun
authors.initials: H
authors.lastname: Gong
mesh_terms: D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000502:physiology*; D045744:Cell Line, Tumor; D004790:Enzyme Induction; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000473:pathology; D015854:Up-Regulation
chemical_list: D016328:NF-kappa B; D051057:Proto-Oncogene Proteins c-akt; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9