Panoply™ Human CDK8 Over-expressing Stable Cell Line

CDK8 is associated with the Mediator transcriptional regulatory complex and has been shown to regulate various cancer-related transcription factors. While CDK8 is an oncogene in pancreatic cancer, its role in cancer angiogenesis remains unclear. Here, researchers aimed to investigate the role of CDK8 in pancreatic cancer angiogenesis and its potential molecular mechanisms. The study showed that CDK8 expression was upregulated in pancreatic cancer tissues compared to adjacent normal tissues, and its expression level was negatively correlated with T stage, liver metastasis, tumor size, lymph node metastasis, and poor prognosis. CDK8 overexpression promoted pancreatic cancer angiogenesis by activating the CDK8-β-catenin-KLF2 signaling pathway, which manifested as upregulation and downregulation of signals related to rate-limiting steps of angiogenesis. In vitro experiments showed that silencing CDK8 inhibited pancreatic cancer angiogenesis. Furthermore, these results were validated in vivo using a nude mouse xenograft model. Therefore, CDK8 promotes pancreatic cancer angiogenesis by activating the CDK8-β-catenin-KLF2 signaling pathway, thus providing an effective target for pancreatic cancer treatment.

CD31 is highly expressed in endothelial cells and can serve as a quantitative marker for angiogenesis. Tumors formed from cells with high CDK8 expression exhibited enhanced angiogenesis compared to tumors formed from cells with low CDK8 expression, as evidenced by a significant increase in microvessel density (MVD). In addition to KLF2, researchers also examined the expression levels of VEGF, CD31, and CDK8 in xenograft tumors using Western blotting and real-time PCR. These xenograft tumors were composed of CDK8-knockdown AsPC-1 and CFPAC-1 cells, as well as CDK8-overexpressing BxPC-3 cells, to assess the relationship of these genes with angiogenesis. CDK8 knockdown resulted in a significant increase in the expression of the inhibitor KLF2. However, the expression of VEGF and CD31 decreased (Figure 1A). Notably, in CDK8-overexpressing BxPC-3 cells, the expression levels of all the aforementioned genes were completely reversed (Figure 1A). The researchers also examined the mRNA expression levels of CDK8, KLF2, VEGF, and CD31 using real-time PCR, and the results were consistent with the Western blotting results (Figure 1B). In summary, these data and previous findings suggest that CDK8 downregulation reduces tumor growth by inhibiting cell proliferation and angiogenesis, while CDK8 upregulation promotes both processes.

Figure 1. Xenografts were harvested, and the expression of KLF2, VEGF, CD31 and CDK8 was assessed for angiogenesis. (Wei R, et al., 2018)