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Stem cell-like properties of CK2β-downregulated mammary cells [miRNA]

ABSTRACT: The ubiquitous Protein kinase CK2 has been demonstrated to be overexpressed in a number of human tumors. This enzyme is composed of two catalytic α or α’ subunits and a dimer of β regulatory subunits whose expression levels are probably implicated in CK2 regulation. Several recent papers reported that unbalanced expression of CK2 subunits is sufficient to drive epithelial to mesenchymal transition, a process involved in cancer invasion and metastasis. Herein, through transcriptomic and miRNA analysis together with comparison of cellular properties between wild type and CK2β-knock-down MCF10A cells, we show that down-regulation of CK2β subunit in mammary epithelial cells induces the acquisition of stem cell-like properties associated with CD44high/CD24low antigenic phenotype and the ability to grow under anchorage-independent conditions. These data demonstrate that a CK2β level establishes a critical cell fate threshold in the control of epithelial cell plasticity. Thus, this regulatory subunit functions as a nodal protein to maintain an epithelial phenotype.

ORGANISM(S): Homo sapiens

PROVIDER: GSE102266 | GEO | 2017/09/05

SECONDARY ACCESSION(S): PRJNA397186

REPOSITORIES: GEO

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Stem cell-like properties of CK2β-downregulated mammary cells [mRNA]

Project description:The ubiquitous Protein kinase CK2 has been demonstrated to be overexpressed in a number of human tumors. This enzyme is composed of two catalytic α or α’ subunits and a dimer of β regulatory subunits whose expression levels are probably implicated in CK2 regulation. Several recent papers reported that unbalanced expression of CK2 subunits is sufficient to drive epithelial to mesenchymal transition, a process involved in cancer invasion and metastasis. Herein, through transcriptomic and miRNA analysis together with comparison of cellular properties between wild type and CK2β-knock-down MCF10A cells, we show that down-regulation of CK2β subunit in mammary epithelial cells induces the acquisition of stem cell-like properties associated with CD44high/CD24low antigenic phenotype and the ability to grow under anchorage-independent conditions. These data demonstrate that a CK2β level establishes a critical cell fate threshold in the control of epithelial cell plasticity. Thus, this regulatory subunit functions as a nodal protein to maintain an epithelial phenotype.

2017-09-05 | GSE102265 | GEO

Substrate selectivity for semisynthetic CK2 proteins with various posttranslational modifications

Project description:Protein Ser/Thr kinase CK2 is involved in a myriad of cellular processes including cell growth and proliferation by phosphorylating hundreds of substrates, yet the regulation process of CK2 function is poorly understood. The CK2 catalytic subunit, CK2α, is modified by O-GlcNAc on Ser347 proximal to a Cdk1 phosphorylation site at Thr344 on the same protein. The substrate selectivity for protein kinase CK2 was examined by performing kinase assays on protein microarrays spotted with 17,000 human proteins. Semisynthetic CK2α proteins were prepared to contain an unmodified C-terminal tail, S-GlcNAc-Serine at S347, or Pfa (non-hyrdolyzeable phosphomimic) at T344. These semisynthetic proteins were used to determine if the posttranslational modifications on CK2 alpha modulate the substrate selectivity for this pleiotropic kinase. The different semisynthetic CK2α proteins were tested alone and in the presence of the regulatory subunit CK2β since it is known that the CK2α subunit is active both in its isolated state and in the heterotetrameric state formed in the presence of the regulatory beta subunit. The CK2β subunit has been shown to modulate CK2 activity with some substrates and not others. In the study presented here, kinase assays were performed using three different semisynthetic CK2 alpha proteins: unmodified C-terminal tail; S-GlcNAc-Ser at 347; and Pfa (phosphomimic) at 344. The semisynthetic proteins were each tested alone and in the presence of the regualatory CK2 beta subunit. There were six different kinase conditions and each condition was performed in duplicate and one no kinase control was performed to eliminate autophorylated proteins.

2011-10-24 | E-GEOD-33149 | biostudies-arrayexpress

CK2β is a gatekeeper of focal adhesions regulating cell spreading

Project description:CK2 is an hetero-tetrameric protein made of two CK2α catalytic subunits and two regulatory CK2β subunits. The free CK2α subunit and the tetrameric holoenzyme have distinct substrate specificity profiles suggesting that the spatiotemporal organization of the individual CK2 subunits observed in living cells is crucial in the control of the many cellular processes that are governed by this pleiotropic kinase. Indeed, sub-stoichiometric expression of CK2β compared to CK2α in a subset of breast cancer tumors was correlated with the induction of EMT markers and increased epithelial cell plasticity in breast carcinoma progression. Using phosphotyrosine profiling with affinity capture and LC/MS-MS, we show that decreased expression of CK2β in MCF10A mammary epithelial cells triggers the phosphorylation of a number of tyrosine phosphorylated proteins and promotes the striking activation of the FAK1-Src-PAX1 signaling pathway. Moreover, morphometric analyses also revealed that CK2β loss increases the number and the spatial distribution of focal adhesion signaling complexes. Together, our finding allows positioning CK2β as a gatekeeper for cell spreading by restraining the focal adhesion maturation and invasion of mammary epithelial cells.

2022-07-05 | PXD030991 | Pride

Ganglioside GD2 identifies Breast Cancer Stem Cells: Targeting GD3 Synthase Inhibits GD2 Expression and Tumor Growth

Project description:We FACS sorted Ras-transformed human mammary epithelial cells (HMLER cells) into GD2+ and GD2- as well as CD44high/CD24low and CD44low/Cd24highcells and comapred the four different population by array. We FACS sorted Ras-transformed human mammary epithelial cells (HMLER cells) into GD2+ and GD2- as well as CD44high/CD24low and CD44low/Cd24highcells and comapred the four different population by array.

2012-04-12 | E-GEOD-36643 | biostudies-arrayexpress

Substrate selectivity for semisynthetic CK2 proteins with various posttranslational modifications

2011-10-25 | GSE33149 | GEO

Ganglioside GD2 identifies Breast Cancer Stem Cells: Targeting GD3 Synthase Inhibits GD2 Expression and Tumor Growth

2012-04-13 | GSE36643 | GEO

Protein Kinase 2 (CK2) Controls CD8+ T-cell Effector and Memory Function during Infection

Project description:Protein kinase 2 (CK2) is a serine/threonine kinase composed of two catalytic subunits (CK2α and/or CK2α') and two regulatory subunits (CK2β). CK2 has been shown to promote cancer progression by regulating the NF-κB, PI3K/AKT/mTOR, JAK/STAT and HIF-1α pathways, and also plays a critical role for immune cell development and function. However, the potential involvement of CK2 in CD8+ T-cell function has not explored. Here, we demonstrate that CK2 protein levels and kinase activity are enhanced upon CD8+ T-cell activation. CK2α deficiency results in impaired CD8+ T-cell activation and proliferation upon TCR stimulation. Furthermore, CK2α is involved in CD8+ T-cell metabolic reprogramming during activation through regulating the AKT/mTOR signaling pathway. Lastly, using a Listeria monocytogenes infection model, we demonstrate that CK2α is required for CD8+ T-cell expansion, maintenance and effector function in both primary and memory immune responses. Taken together, our study implicates CK2 as an important regulator of CD8+ T-cell activation and differentiation both in vitro and in vivo.

2022-06-21 | GSE175941 | GEO

Casein kinase 2 complex: a central regulator of multiple pathobiological signaling pathways in Cryptococcus neoformans

Project description:Casein kinase 2 (CK2) is a potential therapeutic target for several human diseases due to its crucial roles in growth, differentiation, and metabolic homeostasis. This study delves into the role of the CK2 complex in Cryptococcus neoformans, a key fungal pathogen causing meningitis. In C. neoformans, the CK2 complex is made up of a main catalytic subunit (Cka1) and two regulatory subunits (Ckb1 and Ckb2). The primary role of Cka1 is as a protein kinase, while Ckb1/2 assist in various cellular functions. Triple mutants without all three subunits exhibited more pronounced defects than mutants lacking only Cka1, hinting at potential independent functions of Ckb1/2. In animal studies, mutants without these subunits showed a sharp decline in virulence. Moreover, CK2 disruption affected many effector proteins and disrupted key signaling pathways crucial for the pathogenicity of C. neoformans. Overall, the findings highlight the importance of the CK2 complex in fungal biology and its potential as a target for new antifungal treatments.

2023-12-21 | GSE245849 | GEO

Analysis of gene expression changes in fetal erythroid cells obtained from mice with Csnk2b gene conditional deletion in the hematopoietic system.

Project description:Protein Kinase CK2 is a pleiotropic and constitutively expressed enzyme (phosphotransferase) usually present as a tetrameric complex of two catalytic alpha and two regulatory beta subunits. Alpha and beta proteins can also work independently from the holoenzyme exerting different functions on other protein targets. It is well known the CK2 role in promoting cell survival and proliferation and in sustaining the growth of many hematological malignances. However, its physiological role in hematopoiesis, in particular in erythropoiesis is still unknown. Our analysis was focused on the hematopoietic functions of the beta subunit through the generation of conditional KO mice for Csnk2b gene in the hematopoietic system. Our purpose was to asses if CK2b plays a role in the development of erythroid cells. To this aim, we performed a mRNA sequencing analysis of erythroid TER119+ cells purified from control (Csnk2b+/+) and KO (Csnk2b-/-) embryos and here we report a complete list of the genes resulted to be differentially expressed.

2022-09-30 | GSE158665 | GEO

Analysis of gene expression changes in B cells upon Csnk2b conditional deletion

Project description:Protein kinase CK2, a tetrameric enzyme composed by 2 catalitic alpha and 2 regulatory beta subunits, supports malignant B cell lymphocyte growth, however, its physiological role in B lymphopoiesis is still unknown. With this analysis we intended to assess if CK2 plays a role in peripheral B cell development and to do this we compared the mRNA from Csnk2b+/+ (WT) and Csnk2b-/- (KO) purified splenic B cells. Here we report a list of all genes identified as differentially expressed between WT and KO B cells.

2017-12-31 | GSE89082 | GEO

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