A novel selective multikinase inhibitor of ROCK and MRCK effectively blocks cancer cell migration and invasion
| Autor: | Ashley L. Colledge, Shen Shu Sung, Jong K. Yun, Vijay P. Kale, Jeremy A. Hengst, Katherine N. Choe, Yoshinori Takahashi, Taryn E. Dick, Shantu Amin, Dhimant Desai |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
rho-Associated Kinases Stress fiber Kinase Myotonin-protein kinase Cancer Biology medicine.disease Small molecule Article Myotonin-Protein Kinase Oncology Cell culture Cell Movement Cell Line Tumor Neoplasms Cancer cell Cancer research medicine Humans Thiazolidines Neoplasm Invasiveness Protein kinase A Protein Kinase Inhibitors |
| Popis: | Two structurally related protein kinase families, the Rho kinases (ROCK) and the myotonic dystrophy kinase-related Cdc42-binding kinases (MRCK) are required for migration and invasion of cancer cells. We hypothesized that simultaneous targeting of these two kinase families might represent a novel therapeutic strategy to block the migration and invasion of metastatic cancers. To this end, we developed DJ4 as a novel small molecule inhibitor of these kinases. DJ4 potently inhibited activities of ROCK and MRCK in an ATP competitive manner. In cellular functional assays, DJ4 treatment significantly blocked stress fiber formation and inhibited migration and invasion of multiple cancer cell lines in a concentration dependent manner. Our results strongly indicate that DJ4 may be further developed as a novel anti-metastatic chemotherapeutic agent for multiple cancers. |
| Databáze: | OpenAIRE |
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