Protein Kinase CK2—A Putative Target for the Therapy of Diabetes Mellitus?

Ampofo, Emmanuel; Nalbach, Lisa; Menger, Michael D.; Montenarh, Mathias; Götz, Claudia

doi:10.3390/ijms20184398

Cited by 26 publications

(20 citation statements)

References 108 publications

(132 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The role of CK2 in glucose homeostasis is well documented and exerted at multiple levels, i.e., from the control of insulin expression and release to its role in pancreatic β-cell turnover. These and other aspects of the CK2-mediated control of endocrine pancreas physiology have been extensively discussed by Ampofo et al in a recent review [ 172 ].…”

Section: The Role Of Ck2 In Lipid Metabolismmentioning

confidence: 99%

Role of Protein Kinase CK2 in Aberrant Lipid Metabolism in Cancer

Guerra

Issinger

2020

Pharmaceuticals

View full text Add to dashboard Cite

Uncontrolled proliferation is a feature defining cancer and it is linked to the ability of cancer cells to effectively adapt their metabolic needs in response to a harsh tumor environment. Metabolic reprogramming is considered a hallmark of cancer and includes increased glucose uptake and processing, and increased glutamine utilization, but also the deregulation of lipid and cholesterol-associated signal transduction, as highlighted in recent years. In the first part of the review, we will (i) provide an overview of the major types of lipids found in eukaryotic cells and their importance as mediators of intracellular signaling pathways (ii) analyze the main metabolic changes occurring in cancer development and the role of oncogenic signaling in supporting aberrant lipid metabolism and (iii) discuss combination strategies as powerful new approaches to cancer treatment. The second part of the review will address the emerging role of CK2, a conserved serine/threonine protein kinase, in lipid homeostasis with an emphasis regarding its function in lipogenesis and adipogenesis. Evidence will be provided that CK2 regulates these processes at multiple levels. This suggests that its pharmacological inhibition combined with dietary restrictions and/or inhibitors of metabolic targets could represent an effective way to undermine the dependency of cancer cells on lipids to interfere with tumor progression.

show abstract

Section: The Role Of Ck2 In Lipid Metabolismmentioning

confidence: 99%

Role of Protein Kinase CK2 in Aberrant Lipid Metabolism in Cancer

Guerra

Issinger

2020

Pharmaceuticals

View full text Add to dashboard Cite

show abstract

“…With more than 500 substrates, CK2 is involved in various biological processes and estimated to be responsible for up to 10% of the human phosphoproteome [ 2 , 3 ]. CK2 exerts oncogenic activity, because its overexpression promotes tumor development and progression via the activation of proliferation and inhibition of apoptosis [ 4 , 5 , 6 ]. Hence, a broad spectrum of CK2 inhibitors have been developed as potential anti-cancer drugs, including CIGB-300 [ 7 ], 4,5,6,7-tetrabromobenzotriazole (TBB) [ 8 ] and CX-4945 [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

CK2 Activity Mediates the Aggressive Molecular Signature of Glioblastoma Multiforme by Inducing Nerve/Glial Antigen (NG)2 Expression

Schmitt

Boewe

Götz

et al. 2021

Cancers

Self Cite

View full text Add to dashboard Cite

Nerve/glial antigen (NG)2 expression crucially determines the aggressiveness of glioblastoma multiforme (GBM). Recent evidence suggests that protein kinase CK2 regulates NG2 expression. Therefore, we investigated in the present study whether CK2 inhibition suppresses proliferation and migration of NG2-positive GBM cells. For this purpose, CK2 activity was suppressed in the NG2-positive cell lines A1207 and U87 by the pharmacological inhibitor CX-4945 and CRISPR/Cas9-mediated knockout of CK2α. As shown by quantitative real-time PCR, luciferase-reporter assays, flow cytometry and western blot, this significantly reduced NG2 gene and protein expression when compared to vehicle-treated and wild type controls. In addition, CK2 inhibition markedly reduced NG2-dependent A1207 and U87 cell proliferation and migration. The Cancer Genome Atlas (TCGA)-based data further revealed not only a high expression of both NG2 and CK2 in GBM but also a positive correlation between the mRNA expression of the two proteins. Finally, we verified a decreased NG2 expression after CX-4945 treatment in patient-derived GBM cells. These findings indicate that the inhibition of CK2 represents a promising approach to suppress the aggressive molecular signature of NG2-positive GBM cells. Therefore, CX-4945 may be a suitable drug for the future treatment of NG2-positive GBM.

show abstract

“…CK2 has been shown to be critical in embryonic development, differentiation, immunity, cell survival, epithelial homeostasis and circadian rhythms (4)(5)(6)(7). CK2 is also involved in the etiology of many diseases such as multiple sclerosis, cystic fibrosis, chronic intestinal inflammation, cardiac hypertrophy, atherosclerosis, thrombosis, diabetes mellitus, neurological and psychiatric disorders (7)(8)(9)(10)(11). In cancer, although CK2 by itself is not an oncogene, some studies have confirmed the tumorigenic potential of this kinase by regulating cellular processes that are characteristic of malignant transformation such as cell cycle progression, tumor growth and death resistance (12).…”

Section: Introductionmentioning

confidence: 99%

Protein Kinase CK2 in Cancer Energetics

Silva-Pavez

Tapia

2020

Front. Oncol.

View full text Add to dashboard Cite

Protein kinase CK2 (formerly known as casein kinase 2) is abnormally elevated in many cancers. This may increase tumor aggressiveness through CK2-dependent phosphorylation of key proteins in several signaling pathways. In this work, we have compiled evidence from the literature to suggest that CK2 also modulates a metabolic switch characteristic of cancer cells that enhances resistance to death, due to either drugs or to a microenvironment deficient in oxygen or nutrients. Concurrently, CK2 may help to preserve mitochondrial activity in a PTEN-dependent manner. PTEN, widely recognized as a tumor suppressor, is another CK2 substrate in the PI3K/Akt signaling pathway that promotes cancer viability and aerobic glycolysis. Given that CK2 can regulate Akt as well as two of its main effectors, namely mTORC1 and β-catenin, we comprehensively describe how CK2 may modulate cancer energetics by regulating expression of key targets and downstream processes, such as HIF-1 and autophagy, respectively. Thus, the specific inhibition of CK2 may lead to a catastrophic death of cancer cells, which could become a feasible therapeutic strategy to beat this devastating disease. In fact, ATP-competitive inhibitors, synthetic peptides and antisense oligonucleotides have been designed as CK2 inhibitors, some of them used in preclinical models of cancer, of which TBB and silmitasertib are widely known. We will finish by discussing a hypothetical scenario in which cancer cells are "addicted" to CK2; i.e., in which many proteins that regulate signaling pathways and metabolism-linked processes are highly dependent on this kinase.

show abstract

Protein Kinase CK2—A Putative Target for the Therapy of Diabetes Mellitus?

Cited by 26 publications

References 108 publications

Role of Protein Kinase CK2 in Aberrant Lipid Metabolism in Cancer

Role of Protein Kinase CK2 in Aberrant Lipid Metabolism in Cancer

CK2 Activity Mediates the Aggressive Molecular Signature of Glioblastoma Multiforme by Inducing Nerve/Glial Antigen (NG)2 Expression

Protein Kinase CK2 in Cancer Energetics

Contact Info

Product

Resources

About