Up-Regulation of the Alpha Prime Subunit of Protein Kinase CK2 as a Marker of Fast Proliferation in GL261 Cultured Cells

Villamañan, Lucia; Alcaraz, Estefania; Pinna, Lorenzo A.; Ruzzene, Maria; Itarte, Emilio; Arús, Carles; Plana, Maria; Candiota, Ana Paula

doi:10.1007/s12253-018-00567-z

Cited by 6 publications

(4 citation statements)

References 10 publications

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“…77 Interestingly, there are also observations supporting different contribution to the tumor phenotype of the two catalytic isoforms: α′ was found selectively important for osteosarcoma cell proliferation and survival, 78 and the proliferation rate of tumor cells in a murine model of glioblastoma. 79 In contrast, the copy number of the genes for α ( CSNK2A1 ) and β ( CSNK2B ) were found to display gain in breast tumors (~30% and 20%, respectively), 80 while much fewer gains were found on gene for α′ ( CSNK2A2 ). 80 Intriguingly, in the already mentioned study on GN11 cells, α′, while promoting adhesion, reduces migration.…”

Section: Ck2 In Human Diseasesmentioning

confidence: 98%

Protein kinase CK2: a potential therapeutic target for diverse human diseases

Borgo

D’Amore

Sarno

et al. 2021

Sig Transduct Target Ther

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CK2 is a constitutively active Ser/Thr protein kinase, which phosphorylates hundreds of substrates, controls several signaling pathways, and is implicated in a plethora of human diseases. Its best documented role is in cancer, where it regulates practically all malignant hallmarks. Other well-known functions of CK2 are in human infections; in particular, several viruses exploit host cell CK2 for their life cycle. Very recently, also SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has been found to enhance CK2 activity and to induce the phosphorylation of several CK2 substrates (either viral and host proteins). CK2 is also considered an emerging target for neurological diseases, inflammation and autoimmune disorders, diverse ophthalmic pathologies, diabetes, and obesity. In addition, CK2 activity has been associated with cardiovascular diseases, as cardiac ischemia–reperfusion injury, atherosclerosis, and cardiac hypertrophy. The hypothesis of considering CK2 inhibition for cystic fibrosis therapies has been also entertained for many years. Moreover, psychiatric disorders and syndromes due to CK2 mutations have been recently identified. On these bases, CK2 is emerging as an increasingly attractive target in various fields of human medicine, with the advantage that several very specific and effective inhibitors are already available. Here, we review the literature on CK2 implication in different human pathologies and evaluate its potential as a pharmacological target in the light of the most recent findings.

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Section: Ck2 In Human Diseasesmentioning

confidence: 98%

Protein kinase CK2: a potential therapeutic target for diverse human diseases

Borgo

D’Amore

Sarno

et al. 2021

Sig Transduct Target Ther

Self Cite

169

180

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“…In this work, we implanted GL261 cells in the brains of mice to study a preclinical model of glioblastoma. Previous work has established that brain tumors formed from GL261 cells exhibit functional and histologic heterogeneity 27 – 29 , 58 , 59 . The metabolic phenotypes we examined here, however, showed a notable degree of homogeneity at the spatial resolution profiled.…”

Section: Discussionmentioning

confidence: 99%

“…We applied a widely used syngeneic C57BL/6 model of glioblastoma generated by intracerebral injection of GL261 cells harboring a R132H mutation in isocitrate dehydrogenase 1 (IDH1). Prior studies have demonstrated that GL261 tumors exhibit genetic, histologic, and vascular heterogeneity 27 – 29 , but potential changes in metabolic activity throughout the tumor ecosystem have not been well characterized. Moreover, the impact that tumors have on the metabolism of surrounding brain regions comprised of healthy tissue remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Using mass spectrometry imaging to map fluxes quantitatively in the tumor ecosystem

et al. 2023

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Tumors are comprised of a multitude of cell types spanning different microenvironments. Mass spectrometry imaging (MSI) has the potential to identify metabolic patterns within the tumor ecosystem and surrounding tissues, but conventional workflows have not yet fully integrated the breadth of experimental techniques in metabolomics. Here, we combine MSI, stable isotope labeling, and a spatial variant of Isotopologue Spectral Analysis to map distributions of metabolite abundances, nutrient contributions, and metabolic turnover fluxes across the brains of mice harboring GL261 glioma, a widely used model for glioblastoma. When integrated with MSI, the combination of ion mobility, desorption electrospray ionization, and matrix assisted laser desorption ionization reveals alterations in multiple anabolic pathways. De novo fatty acid synthesis flux is increased by approximately 3-fold in glioma relative to surrounding healthy tissue. Fatty acid elongation flux is elevated even higher at 8-fold relative to surrounding healthy tissue and highlights the importance of elongase activity in glioma.

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“…However, several evidences support a possible pro-tumor function of the isolated catalytic subunits [8,9]. The two isoforms α and α' are very similar in structure and often considered overlapping in functions; however, also isoform-specific functions have been described [10,11] and a possible differential role in tumors has been hypothesized [12]. CK2 involvement in cancer has been known since many years, and has been described as a "lateral action", where, by phosphorylating crucial…”

Section: Introductionmentioning

confidence: 99%

Contribution of the CK2 Catalytic Isoforms α and α’ to the Glycolytic Phenotype of Tumor Cells

Zonta

Borgo

Meza

et al. 2021

Cells

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CK2 is a Ser/Thr protein kinase overexpressed in many cancers. It is usually present in cells as a tetrameric enzyme, composed of two catalytic (α or α’) and two regulatory (β) subunits, but it is active also in its monomeric form, and the specific role of the different isoforms is largely unknown. CK2 phosphorylates several substrates related to the uncontrolled proliferation, motility, and survival of cancer cells. As a consequence, tumor cells are addicted to CK2, relying on its activity more than healthy cells for their life, and exploiting it for developing multiple oncological hallmarks. However, little is known about CK2 contribution to the metabolic rewiring of cancer cells. With this study we aimed at shedding some light on it, especially focusing on the CK2 role in the glycolytic onco-phenotype. By analyzing neuroblastoma and osteosarcoma cell lines depleted of either one (α) or the other (α’) CK2 catalytic subunit, we also aimed at disclosing possible pro-tumor functions which are specific of a CK2 isoform. Our results suggest that both CK2 α and α’ contribute to cell proliferation, survival and tumorigenicity. The analyzed metabolic features disclosed a role of CK2 in tumor metabolism, and suggest prominent functions for CK2 α isoform. Results were also confirmed by CK2 pharmacological inhibition. Overall, our study provides new information on the mechanism of cancer cells addiction to CK2 and on its isoform-specific functions, with fundamental implications for improving future therapeutic strategies based on CK2 targeting.

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Up-Regulation of the Alpha Prime Subunit of Protein Kinase CK2 as a Marker of Fast Proliferation in GL261 Cultured Cells

Cited by 6 publications

References 10 publications

Protein kinase CK2: a potential therapeutic target for diverse human diseases

Protein kinase CK2: a potential therapeutic target for diverse human diseases

Using mass spectrometry imaging to map fluxes quantitatively in the tumor ecosystem

Contribution of the CK2 Catalytic Isoforms α and α’ to the Glycolytic Phenotype of Tumor Cells

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