- Authors: Liu, Z., Han, G., Cao, Y., Wang, Y., Gong, H.
- Year: 2014
- Journal: Mol Med Rep 10 2459-64
- Applications: in vitro / DNA / jetPEI
- Cell type: BGC-803
Description: Human gastric cancer cell line.
Calcium/calmodulindependent 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 KN62 decreased gastric cancer cell metastasis. Furthermore, H282R upregulated matrix metalloproteinase9 (MMP9) expression and production, which were dependent on CaMKIImediated increase in nuclear factor (NF)kappaB and Akt activation. Finally, CaMKII activation, through phosphorylation of the Thr 286 site, was significantly increased in the metastatic gastric cancer tissues compared with nonmetastatic 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 NFkappaB and AktmediatedMMP9 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.