CK2 inhibitor CX4945 induces sequential inactivation of proteins in the signaling pathways related with cell migration and suppresses metastasis of A549 human lung cancer cells |
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Authors: | Min Jeong Ku Jong Woo Park Byung Jun Ryu Young-Jin Son Seong Hwan Kim Sang Yeol Lee |
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Institution: | 1. Department of Life Science, Gachon University, San 65, Bokjeong-Dong, Sujeong-Gu, Seongnam-Si, Kyeonggi-Do 461-701, Republic of Korea;2. Laboratory of Translational Therapeutics, Korea Research Institute of Chemical Technology, Yuseong-Gu, Daejeon 305-600, Republic of Korea;3. Department of Pharmacy, Sunchon National University, Suncheon, Jeonnam 540-742, Republic of Korea |
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Abstract: | Casein kinase 2 (CK2) is known to be involved in various cellular processes such as cell cycle, apoptosis and proliferation. It has been reported that the inhibition of CK2 induced by recently developed small molecule CX4945 shows anti-cancer effects including anti-proliferation and anti-angiogenesis in several different cancers including prostate cancer. Here we report that migration and invasion of A549 human lung cancer cells are suppressed by the inhibition of CK2 induced by CX4945. We found that CX4945 sequentially attenuates the proteins in PI3K/Akt and MAPK pathways, two signaling pathways related with cell migration. This sequential control of signal pathways inhibits the expression of membrane type 1-matrix metalloproteinase and this leads to the selective attenuation of one of the gelatinases, MMP-2, which can degrade components of extracellular matrix, and metastasis of A549 human lung cancer cell. |
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Keywords: | CK2 CX-4945 Metastasis Matrix metalloproteinases Human lung cancer |
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