ArticleCarcinogenesis2011
WIF1 is a frequent target for epigenetic silencing in squamous cell carcinoma of the cervix.
Article in Carcinogenesis, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- Kinetic Profiling ofJCO precision oncology · 2024Trial
- Epigenomic characterization of locally advanced anal cancer: a radiation therapy oncology group 98-11 specimen study.Diseases of the colon and rectum · 2014Trial
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- Targeting Wnt Signaling in Endometrial Cancer.Cancers · 2021Review
- Promoter Hypermethylation of Wnt/β-catenin Signaling Pathway InhibitorOman medical journal · 2020Article
- Diagnostic value ofOncotarget · 2018Article
- Preferential epigenetic programming of estrogen response after in utero xenoestrogen (bisphenol-A) exposure.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- Article
- Cervical cancer stem cells.Cell proliferation · 2015Review
- Rapid deamination of cyclobutane pyrimidine dimer photoproducts at TCG sites in a translationally and rotationally positioned nucleosome in vivo.The Journal of biological chemistry · 2015Article
- Targeting the WNT Signaling Pathway in Cancer Therapeutics.The oncologist · 2015Review
- Article
- Global hypomethylation and promoter methylation in small intestinal neuroendocrine tumors: an in vivo and in vitro study.Epigenetics · 2014Article
- Multiplex mapping of chromatin accessibility and DNA methylation within targeted single molecules identifies epigenetic heterogeneity in neural stem cells and glioblastoma.Genome research · 2014Article
- The small splice variant of HPV16 E6, E6, reduces tumor formation in cervical carcinoma xenografts.Virology · 2014Article
- Aberrant methylation of NPY, PENK, and WIF1 as a promising marker for blood-based diagnosis of colorectal cancer.BMC cancer · 2013Article
- HOTAIR, a prognostic factor in esophageal squamous cell carcinoma, inhibits WIF-1 expression and activates Wnt pathway.Cancer science · 2013Article
- DNA methylation and nucleosome occupancy regulate the cancer germline antigen gene MAGEA11.Epigenetics · 2013Article
- Epigenetic diversity of Kaposi's sarcoma-associated herpesvirus.Nucleic acids research · 2013Article
- DNA methyltransferase accessibility protocol for individual templates by deep sequencing.Methods in enzymology · 2012Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Aberrant activation of the Wnt/β-catenin signaling axis is a prominent oncogenic mechanism in numerous cancers including cervical cancer. Wnt inhibitory factor-1 (WIF1) is a secreted protein that binds Wnt and antagonizes Wnt activity. While the WIF1 gene is characterized as a target for epigenetic silencing in some tumor types, WIF1 expression has not been examined in human cervical tissue and cervical cancer. Here, we show that WIF1 is unmethylated and its gene product is expressed in normal cervical epithelium and some cultured cervical tumor lines. In contrast, several cervical cancer lines contained dense CpG methylation within the WIF1 gene, and expression of both WIF1 transcript and protein was restored by culturing cells in the presence of the global DNA demethylating agent 5-aza-2'-deoxycytidine. Using single-molecule MAPit methylation footprinting, we observed differences in chromatin structure within the WIF1 promoter region between cell lines that express and those that do not express WIF1, consistent with transcriptional activity and repression, respectively. The WIF1 promoter was aberrantly methylated in ∼60% (10 of 17) high-grade highly undifferentiated squamous cell cervical tumors examined, whereas paired normal tissue showed significantly lower levels of CpG methylation. WIF1 protein was not detectable by immunohistochemistry in tumors with quantitatively high levels of WIF1 methylation. Of note, WIF1 protein was not detectable in two of the seven unmethylated cervical tumors examined, suggesting other mechanisms may contribute WIF1 repression. Our findings establish the WIF1 gene as a frequent target for epigenetic silencing in squamous cell carcinoma of the cervix.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.