p63 and p73 repress CXCR5 chemokine receptor gene expression in p53-deficient MCF-7 breast cancer cells during genotoxic stress

Mitkin, Nikita A.; Muratova, Alisa M.; Sharonov, George V; Korneev, Kirill V.; Sviriaeva, Ekaterina; Mazurov, Dmitriy; Schwartz, Anton M.; Kuprash, Dmitry V.

doi:10.1016/j.bbagrm.2017.10.003

Cited by 14 publications

(9 citation statements)

References 68 publications

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“…Commercially synthesized single-stranded RNAs (Syntol, Moscow, Russia) were annealed as previously described [ 73 ]. NCIH-196 cells were transfected with siRNA duplexes (500 pmol of per 5 million cells) 48 h before transfection with the luciferase constructs and a further 200 pmol to extend the silencing effect.…”

Section: Methodsmentioning

confidence: 99%

The Risk G Allele of the Single-Nucleotide Polymorphism rs928413 Creates a CREB1-Binding Site That Activates IL33 Promoter in Lung Epithelial Cells

Gorbacheva

Korneev

Kuprash

et al. 2018

IJMS

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Cytokine interleukin 33 (IL-33) is constitutively expressed by epithelial barrier cells, and promotes the development of humoral immune responses. Along with other proinflammatory mediators released by the epithelium of airways and lungs, it plays an important role in a number of respiratory pathologies. In particular, IL-33 significantly contributes to pathogenesis of allergy and asthma; genetic variations in the IL33 locus are associated with increased susceptibility to asthma. Large-scale genome-wide association studies have identified minor “G” allele of the single-nucleotide polymorphism rs928413, located in the IL33 promoter area, as a susceptible variant for early childhood and atopic asthma development. Here, we demonstrate that the rs928413(G) allele creates a binding site for the cAMP response element-binding protein 1 (CREB1) transcription factor. In a pulmonary epithelial cell line, activation of CREB1, presumably via the p38 mitogen-activated protein kinases (MAPK) cascade, activates the IL33 promoter containing the rs928413(G) allele specifically and in a CREB1-dependent manner. This mechanism may explain the negative effect of the rs928413 minor “G” allele on asthma development.

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Section: Methodsmentioning

confidence: 99%

The Risk G Allele of the Single-Nucleotide Polymorphism rs928413 Creates a CREB1-Binding Site That Activates IL33 Promoter in Lung Epithelial Cells

Gorbacheva

Korneev

Kuprash

et al. 2018

IJMS

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“…A CXCR5 promoter analysis revealed that p53 acts indirectly by repressing the activity of NF-κB transcription factors (103). Similar mechanisms for CXCR5 gene regulation may operate upon loss of related tumor suppressors p63 and p73 (104). These studies suggest a potential relationship between genotoxic stress and CXCR5 responses that could have significant prognostic and therapeutic implications in the context of chemotherapy.…”

Section: Cxcl13:cxcr5 Axis In Solid Tumorsmentioning

confidence: 99%

CXCL13 and Its Receptor CXCR5 in Cancer: Inflammation, Immune Response, and Beyond

2019

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It is well-established that the chemokine C-X-C motif ligand 13 (CXCL13) and its receptor, the G-protein coupled receptor (GPCR) CXCR5, play fundamental roles in inflammatory, infectious and immune responses. Originally identified as a B-cell chemoattractant, CXCL13 exerts important functions in lymphoid neogenesis, and has been widely implicated in the pathogenesis of a number of autoimmune diseases and inflammatory conditions, as well as in lymphoproliferative disorders. Current evidence also indicates that the CXCL13:CXCR5 axis orchestrates cell-cell interactions that regulate lymphocyte infiltration within the tumor microenvironment, thereby determining responsiveness to cytotoxic and immune-targeted therapies. In this review, we provide a comprehensive perspective of the involvement of CXCL13 and its receptor in cancer progression. Studies in recent years postulated novel roles for this chemokine in controlling the cancer cell phenotype, and suggest important functions in the growth and metastatic dissemination of solid tumors. Carcinogens have been found to induce CXCL13 production, and production of this chemokine within the tumor milieu has been shown to impact the proliferation, migration, and invasive properties of cancer cells. Thus, the complex networks of cellular interactions involving tumoral CXCL13 and CXCR5 integrate to promote cancer cell autonomous and non-autonomous responses, highlighting the relevance of autocrine and paracrine interactions in dictating the cancer phenotype. Dissecting the molecular and signaling events regulated by CXCL13 and how this chemokine dynamically controls the interaction between the cancer cell and the tumor microenvironment is key to identify novel effectors and therapeutic targets for cancer treatment.

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“…Recently, a new subset of T peripheral helper (Tph) cell populations in RA patients with PD-1 hi CXCR5 − Bcl6 low was identified, which infiltrating inflamed synovia by expressing the chemokine receptor, CCR2, and augmenting synovial B cell responses (84). Interestingly, p53 could repress the CXCR5 chemokine receptor gene via attenuation of NF-κB activity (85), and reduction of BCL6 enhance the DDR pathway. Those studies indicate that DDR pathway exert a strong influence in Tph formation and further studies are expected to examine the DDR signals in Tph subset of RA patients.…”

Section: Impaired Ddr Signals Induce the Disease-related Phenotypes Imentioning

confidence: 99%

DNA Damage Response Signals Transduce Stress From Rheumatoid Arthritis Risk Factors Into T Cell Dysfunction

Shao

2018

Front. Immunol.

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Rheumatoid arthritis (RA) is an autoimmune-mediated disease that is associated with significant cartilage damage and immunosenescence. Despite decades of research, the major signal pathways that initiate RA are still unclear. The DNA damage response (DDR) is a specific and hierarchical network that includes cell cycle checkpoints, DNA repair, and DNA-damage tolerance pathways. Recent studies suggest that this condition is associated with deficits in telomere maintenance and overall genomic instability in the T cells of RA patients. Analysis of the underlying mechanisms has revealed defects in DDR pathways. Particularly, the DNA repair enzyme, ataxia telangiectasia mutated (ATM), is downregulated, which leaves the damaged DNA breaks in RA-associated T cells unrepaired and pushes them to apoptosis, exhausts the T cell pool, and promotes the arthritogenesis effector function of T cells. This review discusses recent advancements and illustrates that risk factors for RA, such as viral infections, environmental events, and genetic risk loci are combat with DDR signals, and the impaired DDR response of RA-associated T cells, in turn, triggers disease-related phenotypes. Therefore, DDR is the dominant signal that converts genetic and environmental stress to RA-related immune dysfunction. Understanding the orchestration of RA pathogenesis by DDR signals would further our current knowledge of RA and provide novel avenues in RA therapy.

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p63 and p73 repress CXCR5 chemokine receptor gene expression in p53-deficient MCF-7 breast cancer cells during genotoxic stress

Cited by 14 publications

References 68 publications

The Risk G Allele of the Single-Nucleotide Polymorphism rs928413 Creates a CREB1-Binding Site That Activates IL33 Promoter in Lung Epithelial Cells

The Risk G Allele of the Single-Nucleotide Polymorphism rs928413 Creates a CREB1-Binding Site That Activates IL33 Promoter in Lung Epithelial Cells

CXCL13 and Its Receptor CXCR5 in Cancer: Inflammation, Immune Response, and Beyond

DNA Damage Response Signals Transduce Stress From Rheumatoid Arthritis Risk Factors Into T Cell Dysfunction

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