ArticleBMC cancer2007
Silencing of the XAF1 gene by promoter hypermethylation in cancer cells and reactivation to TRAIL-sensitization by IFN-beta.
Article in BMC cancer, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 43 citations in OpenAlex.
- XAF1 nonsense mutation rs117407731 enhances lung adenocarcinoma susceptibility via apoptosis suppression.Molecular genetics and genomics : MGG · 2026Article
- XAF1 is secreted from stressed tumor cells to activate T cell-mediated tumor surveillance via Lck-ERK signaling.Neoplasia (New York, N.Y.) · 2025Article
- XAF1 antagonizes TRIM28 activity through the assembly of a ZNF313-mediated destruction complex to suppress tumor malignancy.Molecular biomedicine · 2024Article
- XAF1 Protects Host against Emerging RNA Viruses by Stabilizing IRF1-Dependent Antiviral Immunity.Journal of virology · 2022Article
- XAF1 drives apoptotic switch of endoplasmic reticulum stress response through destabilization of GRP78 and CHIP.Cell death & disease · 2022Article
- Article
- [Effect of stable overexpression of XAF1 gene on biological characteristics of ovarian cancer A2780 cells].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2021Article
- MX2 mediates establishment of interferon response profile, regulates XAF1, and can sensitize melanoma cells to targeted therapy.Cancer medicine · 2021Article
- Review
- ISG12a and its interaction partner NR4A1 are involved in TRAIL-induced apoptosis in hepatoma cells.Journal of cellular and molecular medicine · 2019Article
- C/EBPβ deletion in oncogenic Ras skin tumors is a synthetic lethal event.Cell death & disease · 2018Article
- XAF1 forms a positive feedback loop with IRF-1 to drive apoptotic stress response and suppress tumorigenesis.Cell death & disease · 2018Article
- Identification of XAF1-MT2A mutual antagonism as a molecular switch in cell-fate decisions under stressful conditions.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- iTRAQ-based quantitative proteomics reveals important host factors involved in the high pathogenicity of the H5N1 avian influenza virus in mice.Medical microbiology and immunology · 2017Article
- Tumor suppression in mice lacking GABARAP, an Atg8/LC3 family member implicated in autophagy, is associated with alterations in cytokine secretion and cell death.Cell death & disease · 2016Article
- Epigenetic silencing of the XAF1 gene is mediated by the loss of CTCF binding.Scientific reports · 2015Article
- A novel splice variant of XIAP-associated factor 1 (XAF1) is expressed in peripheral blood containing gastric cancer-derived circulating tumor cells.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2015Article
- XAF1 directs apoptotic switch of p53 signaling through activation of HIPK2 and ZNF313.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- The orally available, synthetic ether lipid edelfosine inhibits T cell proliferation and induces a type I interferon response.PloS one · 2014Article
- ZNF313 is a novel cell cycle activator with an E3 ligase activity inhibiting cellular senescence by destabilizing p21(WAF1.).Cell death and differentiation · 2013Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundXIAP-associated factor 1 (XAF1) is a putative tumor suppressor that exerts its proapoptotic effects through both caspase-dependent and -independent means. Loss of XAF1 expression through promoter methylation has been implicated in the process of tumorigenesis in a variety of cancers. In this report, we investigated the role of basal xaf1 promoter methylation in xaf1 expression and assessed the responsiveness of cancer cell lines to XAF1 induction by IFN-beta.
methodsWe used the conventional bisulfite DNA modification and sequencing method to determine the methylation status in the CpG sites of xaf1 promoter in glioblastoma (SF539, SF295), neuroblastoma (SK-N-AS) and cervical carcinoma (HeLa) cells. We analysed the status and incidence of basal xaf1 promoter methylation in xaf1 expression in non-treated cells as well as under a short or long exposure to IFN-beta. Stable XAF1 glioblastoma knock-down cell lines were established to characterize the direct implication of XAF1 in IFN-beta-mediated sensitization to TRAIL-induced cell death.
resultsWe found a strong variability in xaf1 promoter methylation profile and responsiveness to IFN-beta across the four cancer cell lines studied. At the basal level, aberrant promoter methylation was linked to xaf1 gene silencing. After a short exposure, the IFN-beta-mediated reactivation of xaf1 gene expression was related to the degree of basal promoter methylation. However, in spite of continued promoter hypermethylation, we find that IFN-beta induced a transient xaf1 expression, that in turn, was followed by promoter demethylation upon a prolonged exposure. Importantly, we demonstrated for the first time that IFN-beta-mediated reactivation of endogenous XAF1 plays a critical role in TRAIL-induced cell death since XAF1 knock-down cell lines completely lost their IFN-beta-mediated TRAIL sensitivity.
conclusionTogether, these results suggest that promoter demethylation is not the sole factor determining xaf1 gene induction under IFN-beta treatment. Furthermore, our study provides evidence that XAF1 is a crucial interferon-stimulated gene (ISG) mediator of IFN-induced sensitization to TRAIL in cancer.
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