CK2 genes are overexpressed in many human cancers, and most often overexpression is associated with worse prognosis. Site-specific expression in mice leads to cancer development (e.g., breast, lymphoma) indicating the oncogenic nature of CK2. CK2 is involved in many key aspects of cancer including inhibition of apoptosis, modulation of signaling pathways, DNA damage response, and cell cycle regulation. A number of CK2 inhibitors are now available and have been shown to have activity against various cancers in vitro and in pre-clinical models. Some of these inhibitors are now undergoing exploration in clinical trials as well. In this review, we will examine some of the major cancers in which CK2 inhibition has promise based on in vitro and pre-clinical studies, the proposed cellular and signaling mechanisms of anti-cancer activity by CK2 inhibitors, and the current or recent clinical trials using CK2 inhibitors.

Cancer is a leading cause of death worldwide. Cancer cells proliferate uncontrollably and, many cases, spread to other parts of the body. A protein historically involved in cancer is protein kinase CK2. CK2 is a serine-threonine kinase that has been involved in cell growth, cell proliferation and cell apoptosis. CK2 functions as an oncogene when overexpressed in mouse tissues, and can synergize with known oncogenes, such as ras, to induce cell transformation in cells in culture. CK2, typically the CK2α protein, is found elevated in a number of human tumors. However, we have little information on CK2α' and CK2β proteins, and scarce information on CK2 gene transcript expression. Here, we explore the expression of CK2 transcripts in primary tumor tissues using the database Oncomine in the six cancers with the highest mortality in the U.S.A. In addition, we studied the correlation between CK2 expression and overall survival using the Kaplan-Meier Plotter database in breast, ovarian, and lung cancers. We found widespread upregulation in the expression of CK2 genes in primary tumor tissues. However, we found underexpression of CK2α' transcripts in some tumors, increased CK2β transcripts in some invasive tumors, and deregulation of CK2 transcripts in some tumor precursors. There was also correlation between CK2 expression levels and patient survival. These data provides additional evidence for CK2 as a biomarker for cancer studies and as a target for cancer therapy.

A multitude of proteins are aberrantly expressed in cancer cells, including the oncogenic serine-threonine kinase CK2. In a previous report, we found increases in CK2 transcript expression that could explain the increased CK2 protein levels found in tumors from lung and bronchus, prostate, breast, colon and rectum, ovarian and pancreatic cancers. We also found that, contrary to the current notions about CK2, some CK2 transcripts were downregulated in several cancers. Here, we investigate all other cancers using Oncomine to determine whether they also display significant CK2 transcript dysregulation. As anticipated from our previous analysis, we found cancers with all CK2 transcripts upregulated (e.g. cervical), and cancers where there was a combination of upregulation and/or downregulation of the CK2 transcripts (e.g. sarcoma). Unexpectedly, we found some cancers with significant downregulation of all CK2 transcripts (e.g. testicular cancer). We also found that, in some cases, CK2 transcript levels were already dysregulated in benign lesions (e.g. Barrett’s esophagus). We also found that CK2 transcript upregulation correlated with lower patient survival in most cases where data was significant. However, there were two cancer types, glioblastoma and renal cell carcinoma, where CK2 transcript upregulation correlated with higher survival. Overall, these data show that the expression levels of CK2 genes is highly variable in cancers and can lead to different patient outcomes.

Recent studies have demonstrated the activation of phospholipase C-mediated hydrolysis of phosphatidylcholine both by growth factors and by the product of ras oncogene, ras p21. Also, evidence has been presented indicating that the stimulation of this phospholipid-degradative pathway is sufficient to activate mitogenesis in fibroblasts. In Xenopus laevis oocytes, microinjection of transforming ras p21 is a potent inducer of maturation, whereas microinjection of a neutralizing anti-ras p21 antibody specifically inhibits maturation induced by insulin but not by progesterone. The results presented here demonstrated that microinjection of phosphatidylcholine-hydrolyzing phospholipase C is sufficient to induce maturation of Xenopus laevis oocytes. Furthermore, microinjection of a neutralizing anti-phosphatidylcholine-hydrolyzing phospholipase C specifically blocks the maturation program induced by ras p21/insulin but not by progesterone.

Basic science educators are not trained as clinicians, yet are expected to adjust their content to mesh appropriately with its clinical application. While achievable, this is a challenge that requires intentional effort on the part of the basic science educators. A practical solution to facilitate curricular integration is to create experiential opportunities for basic scientists to observe the clinical application of their content and to pair these initiatives with training in effective medical education practices.

Mouse embryonic fibroblast (MEF) cells are an important in vitro model for developmental biology, disease, and reprogramming studies. However, as with other primary cells, they are challenging to transfect. Although viral gene-delivery methods achieve ...