RAP1/TERF2IP—A Multifunctional Player in Cancer Development

Deręgowska, Anna; Wnuk, Maciej

doi:10.3390/cancers13235970

Cited by 21 publications

(14 citation statements)

References 88 publications

(147 reference statements)

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“…Moreover, contrary to the other researchers we have shown a positive correlation between increased expression of TRF2, RAP1, TTP1, TNKS1, and TNKS2 genes and the level of expression of BCR::ABL1, and also simultaneously with a decrease in the length of telomeres. Nevertheless, one ought to remember that an increase in the expression of RAP1 observed here may not be related to changes in telomeres and could be merely another form of adaptation of CML cells to increased metabolic activity characteristic for cancer cells (Deregowska and Wnuk 2021). It is well known that RAP1 is a pleiotropic protein that is responsible for the regulation of cell metabolism, the production of conditions associated with inflammation, response to oxidative stress (Cai et al 2017) and regulation of hematopoietic stem cell survival (Khattar et al 2019).…”

Section: Discussionmentioning

confidence: 85%

The interplay between telomeric complex members and BCR::ABL1 oncogenic tyrosine kinase in the maintenance of telomere length in chronic myeloid leukemia

Deręgowska

Pepek

Solarska

et al. 2023

J Cancer Res Clin Oncol

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Purpose Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by recurrent genetic aberration in leukemic stem cells, namely Philadelphia chromosome caused by reciprocal translocation t(9;22)(q34;q11). In our study, we analyzed the telomeric complex expression and function in the molecular pathogenesis of CML. Methods We employed CD34+ primary leukemic cells, comprising both leukemic stem and progenitor cell populations, isolated from peripheral blood or bone marrow of CML patients in chronic and blastic phase to analyze the telomere length and telomeric-associated proteins. Results The reduction in telomere length during disease progression was correlated with increased expression of BCR::ABL1 transcript and the dynamic changes were neither associated with the enzymatic activity of telomerase nor with gene copy number and expression of telomerase subunits. Increased expression of BCR::ABL1 was positively correlated with expression of TRF2, RAP1, TPP1, DKC1, TNKS1, and TNKS2 genes. Conclusions The dynamics of telomere length changes in CD34+ CML cells is dependent on the expression level of BCR::ABL, which promotes the expression of certain shelterins including RAP1 and TRF2, as well as TNKS, and TNKS2, and results in telomere shortening regardless of telomerase activity. Our results may allow better understanding of the mechanisms responsible for the genomic instability of leukemic cells and CML progression.

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Section: Discussionmentioning

confidence: 85%

The interplay between telomeric complex members and BCR::ABL1 oncogenic tyrosine kinase in the maintenance of telomere length in chronic myeloid leukemia

Deręgowska

Pepek

Solarska

et al. 2023

J Cancer Res Clin Oncol

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“…Whether these ETS2 family transcription factors can be recruited to bind GABPA binding sites in response to the combined antigen and IL-33 stimulation remains to be determined. RAP1 is encoded by a gene named TERF2IP (Deregowska and Wnuk 2021). RAP1 interacts with transcription factor TERF2 to binds consensus sequences TTAGGG found next to AP1, NF-κB and GABPA binding sites (Arat and Griffith 2012).…”

Section: Discussionmentioning

confidence: 99%

IL-33 priming and antigenic stimulation synergistically promote the transcription of proinflammatory cytokine and chemokine genes in human skin mast cells

Gao

Guan

et al. 2022

Preprint

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Antigenic stimulation through cross-linking the IgE receptor and epithelial cell-derived cytokine IL-33 are potent stimuli of mast cell (MC) activation. However, target genes induced by the combined antigen and IL-33 stimulation have not been investigated in human skin mast cells in a genome-wide manner. Furthermore, epigenetic mechanisms by which IL-33 acts synergically with antigenic stimulation to induce gene transcription have not been investigated. We identified the target genes that responded to the combined antigen and IL-33 stimulation using RNA-seq. These genes can be divided into three groups. Genes in the first group are target genes where antigenic stimulation and IL-33 stimulation achieve high levels of synergy in promoting these gene transcription (high synergy target genes). Genes in the second group are target genes for low levels of synergy mediated by the combined antigen and IL-33 stimulation (low synergy target genes). And genes in the third group are not targeted for the antigen and IL-33 synergy (non-synergy target genes). We found that pro-inflammatory cytokine and chemokine genes were enriched among the high synergy target genes. We demonstrate that the combined antigen and IL-33 stimulation-induced or -increased chromatin accessible areas in the regulatory regions of the high synergy target genes but not of the low synergy target genes. Transcription factor binding motif analysis revealed more binding sites for NF-κB, AP-1, GABPA, and RAP1 in the induced or increased chromatin accessible regions of the high synergy target genes. Our study shines a light on an epigenetic mechanism by which how epithelial cell-derived cytokine IL-33 might cause exacerbation of skin MC-mediated allergic inflammation.

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“…TERF2IP (also known as RAP1), a member of the shelterin complex, plays a crucial part in protecting telomeric function and maintaining chromosome stability. It also acts as an essential modulator to enhance NF-kB signaling and attenuate STAT3 signaling [ 81 , 115 ]. Of note, activating the NF-κB pathway and the STAT3 pathway can induce M1 and M2 gene expression, respectively [ 22 , 116 , 117 ].…”

Section: Hypoxia-driven Crosstalk Between Tumor Cells and Tamsmentioning

confidence: 99%

The hypoxia-driven crosstalk between tumor and tumor-associated macrophages: mechanisms and clinical treatment strategies

et al. 2022

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Given that hypoxia is a persistent physiological feature of many different solid tumors and a key driver for cancer malignancy, it is thought to be a major target in cancer treatment recently. Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment (TME), which have a large impact on tumor development and immunotherapy. TAMs massively accumulate within hypoxic tumor regions. TAMs and hypoxia represent a deadly combination because hypoxia has been suggested to induce a pro-tumorigenic macrophage phenotype. Hypoxia not only directly affects macrophage polarization, but it also has an indirect effect by altering the communication between tumor cells and macrophages. For example, hypoxia can influence the expression of chemokines and exosomes, both of which have profound impacts on the recipient cells. Recently, it has been demonstrated that the intricate interaction between cancer cells and TAMs in the hypoxic TME is relevant to poor prognosis and increased tumor malignancy. However, there are no comprehensive literature reviews on the molecular mechanisms underlying the hypoxia-mediated communication between tumor cells and TAMs. Therefore, this review has the aim to collect all recently available data on this topic and provide insights for developing novel therapeutic strategies for reducing the effects of hypoxia.

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RAP1/TERF2IP—A Multifunctional Player in Cancer Development

Cited by 21 publications

References 88 publications

The interplay between telomeric complex members and BCR::ABL1 oncogenic tyrosine kinase in the maintenance of telomere length in chronic myeloid leukemia

The interplay between telomeric complex members and BCR::ABL1 oncogenic tyrosine kinase in the maintenance of telomere length in chronic myeloid leukemia

IL-33 priming and antigenic stimulation synergistically promote the transcription of proinflammatory cytokine and chemokine genes in human skin mast cells

The hypoxia-driven crosstalk between tumor and tumor-associated macrophages: mechanisms and clinical treatment strategies

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