CK2: A Global Regulator of Cell Death

Trembley, Janeen H.; Qaiser, Fatima; Kren, Betsy T.; Ahmed, Khalil

doi:10.1007/978-3-319-14544-0_10

Cited by 3 publications

(2 citation statements)

References 134 publications

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“…CK2 is elevated during normal cell proliferation; however, it demonstrates an increased persistent expression at the protein level in cancer cells [8,10,11,12]. Besides its role in cell growth and proliferation, CK2 also functions to suppress cell death—this aspect may reflect one of the most significant functions of CK2, especially with respect to its role in cancer biology [16,17,18,19].…”

Section: Introductionmentioning

confidence: 99%

CK2 Pro-Survival Role in Prostate Cancer Is Mediated via Maintenance and Promotion of Androgen Receptor and NFκB p65 Expression

et al. 2019

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The prosurvival protein kinase CK2, androgen receptor (AR), and nuclear factor kappa B (NFκB) interact in the function of prostate cells, and there is evidence of crosstalk between these signals in the pathobiology of prostate cancer (PCa). As CK2 is elevated in PCa, and AR and NFκB are involved in the development and progression of prostate cancer, we investigated their interaction in benign and malignant prostate cells in the presence of altered CK2 expression. Our results show that elevation of CK2 levels caused increased levels of AR and NFκB p65 in prostate cells of different phenotypes. Analysis of TCGA PCa data indicated that AR and CK2α RNA expression are strongly correlated. Small molecule inhibition or molecular down-regulation of CK2 caused reduction in AR mRNA expression and protein levels in PCa cells and in orthotopic xenograft tumors by various pathways. Among these, regulation of AR protein stability plays a unifying role in CK2 maintenance of AR protein levels. Our results show induction of various endoplasmic reticulum stress signals after CK2 inhibition, which may play a role in the PCa cell death response. Of note, CK2 inhibition caused loss of cell viability in both parental and enzalutamide-resistant castrate-resistant PCa cells. The present work elucidates the specific link of CK2 to the pathogenesis of PCa in association with AR and NFκB expression; further, the observation that inhibition of CK2 can exert a growth inhibitory effect on therapy-resistant PCa cells emphasizes the potential utility of CK2 inhibition in patients who are on enzalutamide treatment for advanced cancer.

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Section: Introductionmentioning

confidence: 99%

CK2 Pro-Survival Role in Prostate Cancer Is Mediated via Maintenance and Promotion of Androgen Receptor and NFκB p65 Expression

et al. 2019

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“…Over time, several investigations recognized the association of protein kinase CK2 with cell growth and proliferation in normal and cancer cells (reviewed in, e.g., [ 1 , 4 , 5 , 6 , 7 ]). However, its link to cancer biology was firmly established only when it was discovered that CK2 not only promotes cell growth and proliferation but also is an effective suppressor of cell death, originally revealed by this laboratory [ 8 , 9 , 10 , 11 ]. Likewise, it was recognized that the treatment of cells with antisense to CK2 resulted in potent cell death, thus prompting the notion, for the first time, that CK2 downregulation might serve as cancer therapy strategy [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

CK2 Molecular Targeting—Tumor Cell-Specific Delivery of RNAi in Various Models of Cancer

et al. 2017

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Protein kinase CK2 demonstrates increased protein expression relative to non-transformed cells in the majority of cancers that have been examined. The elevated levels of CK2 are involved in promoting not only continued proliferation of cancer cells but also their resistance to cell death; thus, CK2 has emerged as a plausible target for cancer therapy. Our focus has been to target CK2 catalytic subunits at the molecular level using RNA interference (RNAi) strategies to achieve their downregulation. The delivery of oligonucleotide therapeutic agents warrants that they are protected and are delivered specifically to cancer cells. The latter is particularly important since CK2 is a ubiquitous signal that is essential for survival. To achieve these goals, we have developed a nanocapsule that has the properties of delivering an anti-CK2 RNAi therapeutic cargo, in a protected manner, specifically to cancer cells. Tenfibgen (TBG) is used as the ligand to target tenascin-C receptors, which are elevated in cancer cells. This strategy is effective for inhibiting growth and inducing death in several types of xenograft tumors, and the nanocapsule elicits no safety concerns in animals. Further investigation of this therapeutic approach for its translation is warranted.

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Protein kinase CK2 impact on intracellular calcium homeostasis in prostate cancer

et al. 2020

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CK2: A Global Regulator of Cell Death

Cited by 3 publications

References 134 publications

CK2 Pro-Survival Role in Prostate Cancer Is Mediated via Maintenance and Promotion of Androgen Receptor and NFκB p65 Expression

CK2 Pro-Survival Role in Prostate Cancer Is Mediated via Maintenance and Promotion of Androgen Receptor and NFκB p65 Expression

CK2 Molecular Targeting—Tumor Cell-Specific Delivery of RNAi in Various Models of Cancer

Protein kinase CK2 impact on intracellular calcium homeostasis in prostate cancer

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