CDK8

Clinical significance

CDK8 is a colorectal cancer oncogene: the CDK8 gene is amplified in human colorectal tumors, activating β-catenin-mediated transcription that drives colon tumorigenesis. However, CDK8 may not be oncogenic in all cell types, and indeed may act as a tumor suppressor in the notch and EGFR signaling pathways. Specifically, CDK8 promotes turnover of the notch intracellular domain, and inhibits EGFR signaling-driven cell fates in C. elegans. Thus, CDK8 may be an oncogene in cancers driven by Wnt/β-catenin signaling, but could instead be a tumor suppressor gene in cancers driven by notch or EGFR signaling. In addition, CDK8 promotes transcriptional activation mediated by the tumor suppressor protein p53, indicating that it may have an important role in tumor suppression Further research is needed to delineate the effects of CDK8 inhibition in different tissues, so for the time being, drugs targeting CDK8 for cancer treatment remain untested in humans.