title: 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.
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.
authors.affiliation: Department of Life Science, Gachon University, San 65, Bokjeong-Dong, Sujeong-Gu, Seongnam-Si, Kyeonggi-Do 461-701, Republic of Korea.
authors.forename: Min Jeong
authors.initials: MJ
authors.lastname: Ku
authors.forename: Jong Woo
authors.initials: JW
authors.lastname: Park
authors.forename: Byung Jun
authors.initials: BJ
authors.lastname: Ryu
authors.forename: Young-Jin
authors.initials: YJ
authors.lastname: Son
authors.forename: Seong Hwan
authors.initials: SH
authors.lastname: Kim
authors.forename: Sang Yeol
authors.initials: SY
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000633:toxicity; D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009287:Naphthyridines / Q000737:chemistry* / Q000633:toxicity; D010619:Phenazines; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D047390:Casein Kinase II; D018093:Gelatinases; D020781:Matrix Metalloproteinase 1; D020778:Matrix Metalloproteinase 2; D020929:Mitogen-Activated Protein Kinase Kinases; D009287:Naphthyridines; D010619:Phenazines; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C555142:silmitasertib
keywords: CK2; CX-4945; Human lung cancer; Matrix metalloproteinases; Metastasis