Effects of altered expression and activity levels of casein kinase 1 and on tumor growth and survival of colorectal cancer patients

Colorectal cancer (CRC) is the fourth leading cause of cancer-related death worldwide due to high apoptotic resistance and metastatic potential. Since mutations as well as deregulation of CK1 isoforms contribute to tumor development and progression, CK1 has become an interesting drug target. In this study, we show that CK1 isoforms are differently expressed in colon tumor cell lines and that growth of these cell lines can be inhibited by CK1-specific inhibitors. Furthermore, expression of CK1 and is changed in colorectal tumors and high CK1 expression levels significantly correlate with prolonged patients' survival. In addition to changes in CK1 and expression, mutations within exon 3 of CK1 were detected in colorectal tumors. These mutations influence ATP binding, leading to changes in the kinetic parameters.

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