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1
Epigenetic alteration of the Wnt inhibitory factor-1 promoter occurs early in the carcinogenesis of Barrett's esophagus.Wnt抑制因子1启动子的表观遗传改变在巴雷特食管癌变早期就会出现。
Cancer Sci. 2008 Jan;99(1):46-53. doi: 10.1111/j.1349-7006.2007.00663.x. Epub 2007 Nov 13.
2
Hypermethylation of the AKAP12 promoter is a biomarker of Barrett's-associated esophageal neoplastic progression.AKAP12启动子的高甲基化是巴雷特食管相关肿瘤进展的生物标志物。
Cancer Epidemiol Biomarkers Prev. 2008 Jan;17(1):111-7. doi: 10.1158/1055-9965.EPI-07-0407.
3
Alterations of the Wnt signaling pathway during the neoplastic progression of Barrett's esophagus.巴雷特食管肿瘤进展过程中Wnt信号通路的改变。
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4
Subtypes of Barrett's oesophagus and oesophageal adenocarcinoma based on genome-wide methylation analysis.基于全基因组甲基化分析的 Barrett 食管和食管腺癌亚型。
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5
Frequent epigenetic inactivation of Wnt inhibitory factor-1 in human gastrointestinal cancers.Wnt抑制因子-1在人类胃肠道癌症中频繁发生表观遗传失活。
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7
In-depth characterization of the Wnt-signaling/β-catenin pathway in an in vitro model of Barrett's sequence.在巴雷特食管序列的体外模型中对Wnt信号/β-连环蛋白通路进行深入表征。
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Temporal evolution in caveolin 1 methylation levels during human esophageal carcinogenesis.人食管癌发生过程中小窝蛋白1甲基化水平的时间演变
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Hypomethylation of noncoding DNA regions and overexpression of the long noncoding RNA, AFAP1-AS1, in Barrett's esophagus and esophageal adenocarcinoma.非编码 DNA 区域的低甲基化和长非编码 RNA AFAP1-AS1 在 Barrett 食管和食管腺癌中的过表达。
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The Wnt signaling pathway in tumorigenesis, pharmacological targets, and drug development for cancer therapy.Wnt信号通路在肿瘤发生、药理学靶点及癌症治疗药物研发中的作用
Biomark Res. 2021 Sep 6;9(1):68. doi: 10.1186/s40364-021-00323-7.
2
Meta-Analysis Based on Nonconvex Regularization.基于非凸正则化的荟萃分析。
Sci Rep. 2020 Apr 1;10(1):5755. doi: 10.1038/s41598-020-62473-2.
3
Dickkopf-1 (DKK1) promotes tumor growth via Akt-phosphorylation and independently of Wnt-axis in Barrett's associated esophageal adenocarcinoma.迪克kopf-1（DKK1）通过Akt磷酸化促进肿瘤生长，且在巴雷特食管相关腺癌中与Wnt轴无关。
Am J Cancer Res. 2019 Feb 1;9(2):330-346. eCollection 2019.
4
In-depth characterization of the Wnt-signaling/β-catenin pathway in an in vitro model of Barrett's sequence.在巴雷特食管序列的体外模型中对Wnt信号/β-连环蛋白通路进行深入表征。
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5
A systematic review of epigenetic biomarkers in progression from non-dysplastic Barrett's oesophagus to oesophageal adenocarcinoma.非异型增生性 Barrett 食管进展为食管腺癌的表观遗传生物标志物的系统评价。
BMJ Open. 2018 Jun 30;8(6):e020427. doi: 10.1136/bmjopen-2017-020427.
6
Correlations of Promoter Methylation in WIF-1, RASSF1A, and CDH13 Genes with the Risk and Prognosis of Esophageal Cancer.WIF-1、RASSF1A和CDH13基因启动子甲基化与食管癌风险及预后的相关性
Med Sci Monit. 2016 Aug 10;22:2816-24. doi: 10.12659/msm.896877.
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Wnt/β-Catenin Signaling Activation beyond Robust Nuclear β-Catenin Accumulation in Nondysplastic Barrett's Esophagus: Regulation via Dickkopf-1.Wnt/β-连环蛋白信号激活在非发育异常的巴雷特食管中超越了强大的核β-连环蛋白积累：通过Dickkopf-1进行调控
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8
Inhibition of Notch signaling enhances transdifferentiation of the esophageal squamous epithelium towards a Barrett's-like metaplasia via KLF4.Notch信号通路的抑制通过KLF4增强食管鳞状上皮向巴雷特样化生的转分化。
Cell Cycle. 2014;13(24):3857-66. doi: 10.4161/15384101.2014.972875.
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WIF1 causes dysfunction of heart in transgenic mice.WIF1 导致转基因小鼠心脏功能障碍。
Transgenic Res. 2013 Dec;22(6):1179-89. doi: 10.1007/s11248-013-9738-z. Epub 2013 Aug 7.
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Signaling pathways in the molecular pathogenesis of adenocarcinomas of the esophagus and gastroesophageal junction.食管及胃食管交界腺癌分子发病机制中的信号通路
Cancer Biol Ther. 2013 Sep;14(9):782-95. doi: 10.4161/cbt.25362. Epub 2013 Jun 17.

本文引用的文献

1
The tumor suppressor Wnt inhibitory factor 1 is frequently methylated in nasopharyngeal and esophageal carcinomas.肿瘤抑制因子Wnt抑制因子1在鼻咽癌和食管癌中经常发生甲基化。
Lab Invest. 2007 Jul;87(7):644-50. doi: 10.1038/labinvest.3700547. Epub 2007 Mar 26.
2
Wnt inhibitory factor-1, a Wnt antagonist, is silenced by promoter hypermethylation in malignant pleural mesothelioma.Wnt抑制因子-1，一种Wnt拮抗剂，在恶性胸膜间皮瘤中因启动子高甲基化而沉默。
Biochem Biophys Res Commun. 2006 Apr 21;342(4):1228-32. doi: 10.1016/j.bbrc.2006.02.084. Epub 2006 Feb 24.
3
Inactivation of Wnt inhibitory factor-1 (WIF1) expression by epigenetic silencing is a common event in breast cancer.通过表观遗传沉默使Wnt抑制因子1（WIF1）表达失活在乳腺癌中是常见现象。
Carcinogenesis. 2006 Jul;27(7):1341-8. doi: 10.1093/carcin/bgi379. Epub 2006 Feb 25.
4
Epigenetic inactivation of Wnt inhibitory factor-1 plays an important role in bladder cancer through aberrant canonical Wnt/beta-catenin signaling pathway.Wnt抑制因子-1的表观遗传失活通过异常的经典Wnt/β-连环蛋白信号通路在膀胱癌中起重要作用。
Clin Cancer Res. 2006 Jan 15;12(2):383-91. doi: 10.1158/1078-0432.CCR-05-1344.
5
Wnt signaling activation and WIF-1 silencing in nasopharyngeal cancer cell lines.鼻咽癌细胞系中的Wnt信号激活与WIF-1沉默
Biochem Biophys Res Commun. 2006 Mar 10;341(2):635-40. doi: 10.1016/j.bbrc.2005.12.220. Epub 2006 Jan 17.
6
Alterations of the Wnt signaling pathway during the neoplastic progression of Barrett's esophagus.巴雷特食管肿瘤进展过程中Wnt信号通路的改变。
Oncogene. 2006 May 18;25(21):3084-92. doi: 10.1038/sj.onc.1209338.
7
Methylation of APC, TIMP3, and TERT: a new predictive marker to distinguish Barrett's oesophagus patients at risk for malignant transformation.APC、TIMP3和TERT的甲基化：一种区分有恶变风险的巴雷特食管患者的新预测标志物。
J Pathol. 2006 Jan;208(1):100-7. doi: 10.1002/path.1884.
8
Inhibition of Wnt16 in human acute lymphoblastoid leukemia cells containing the t(1;19) translocation induces apoptosis.在含有t(1;19)易位的人急性淋巴母细胞白血病细胞中抑制Wnt16可诱导细胞凋亡。
Oncogene. 2005 Aug 11;24(34):5396-400. doi: 10.1038/sj.onc.1208568.
9
Frequent epigenetic inactivation of Wnt inhibitory factor-1 in human gastrointestinal cancers.Wnt抑制因子-1在人类胃肠道癌症中频繁发生表观遗传失活。
Oncogene. 2005 Nov 24;24(53):7946-52. doi: 10.1038/sj.onc.1208910.
10
Wnt2 as a new therapeutic target in malignant pleural mesothelioma.
Int J Cancer. 2005 Nov 1;117(2):326-32. doi: 10.1002/ijc.21160.

Wnt抑制因子1启动子的表观遗传改变在巴雷特食管癌变早期就会出现。

Epigenetic alteration of the Wnt inhibitory factor-1 promoter occurs early in the carcinogenesis of Barrett's esophagus.

作者信息

Clément Geneviève, Guilleret Isabelle, He Biao, Yagui-Beltrán Adam, Lin Yu-Ching, You Liang, Xu Zhidong, Shi Yihui, Okamoto Junichi, Benhattar Jean, Jablons David

机构信息

Thoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center, University of California San Francisco, 2340 Sutter St, San Francisco, CA 94115, USA.

出版信息

Cancer Sci. 2008 Jan;99(1):46-53. doi: 10.1111/j.1349-7006.2007.00663.x. Epub 2007 Nov 13.

DOI:10.1111/j.1349-7006.2007.00663.x
PMID:18005197
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11158554/
Abstract

The role of Wnt antagonists in the carcinogenesis of esophageal adenocarcinoma (EAC) remains unclear. We hypothesized that downregulation of the Wnt inhibitory factor-1 (WIF-1) might be involved in the neoplastic progression of Barrett's esophagus (BE). We analyzed the DNA methylation status of the WIF-1 promoter in normal, preneoplastic, and neoplastic samples from BE patients and in EAC cell lines. We investigated the role of WIF-1 on EAC cell growth and the chemosensitization of the cells to cisplatin. We found that silencing of WIF-1 correlated with promoter hypermethylation. EAC tissue samples showed higher levels of WIF-1 methylation compared to the matched normal epithelium. In addition, we found that WIF-1 hypermethylation was more frequent in BE samples from patients with EAC than in BE samples from patients who had not progressed to EAC. Restoration of WIF-1 in cell lines where WIF-1 was methylation-silenced resulted in growth suppression. Restoration of WIF-1 could sensitize the EAC cells to the chemotherapy drug cisplatin. Our results suggest that silencing of WIF-1 through promoter hypermethylation is an early and common event in the carcinogenesis of BE. Restoring functional WIF-1 might be used as a new targeted therapy for the treatment of this malignancy.

摘要

Wnt拮抗剂在食管腺癌（EAC）致癌过程中的作用仍不清楚。我们推测，Wnt抑制因子-1（WIF-1）的下调可能参与了巴雷特食管（BE）的肿瘤进展。我们分析了BE患者的正常、癌前和肿瘤样本以及EAC细胞系中WIF-1启动子的DNA甲基化状态。我们研究了WIF-1对EAC细胞生长的作用以及细胞对顺铂的化学增敏作用。我们发现WIF-1的沉默与启动子高甲基化相关。与匹配的正常上皮相比，EAC组织样本显示出更高水平的WIF-1甲基化。此外，我们发现EAC患者的BE样本中WIF-1高甲基化比未进展为EAC的患者的BE样本中更常见。在WIF-1因甲基化而沉默的细胞系中恢复WIF-1会导致生长抑制。恢复WIF-1可使EAC细胞对化疗药物顺铂敏感。我们的结果表明，通过启动子高甲基化使WIF-1沉默是BE致癌过程中的一个早期常见事件。恢复功能性WIF-1可能用作治疗这种恶性肿瘤的一种新的靶向疗法。