ArticleClinical cancer research : an official journal of the American Association for Cancer Research2013
Promoter hypomethylation of EpCAM-regulated bone morphogenetic protein gene family in recurrent endometrial cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 39 citations in OpenAlex.
- EpCAM Signaling in Oral Cancer Stem Cells: Implications for Metastasis, Tumorigenicity, and Therapeutic Strategies.Current issues in molecular biology · 2025Review
- Comprehensive DNA methylation profiling by MeDIP-NGS identifies potential genes and pathways for epithelial ovarian cancer.Journal of ovarian research · 2024Article
- SIM2: Its Prognostic Significance and Oncogenic Role in Endometrial Carcinoma.OncoTargets and therapy · 2024Article
- Bone morphogenetic protein signaling is a possible therapeutic target in gynecologic cancer.Cancer science · 2023Review
- Understanding the versatile roles and applications of EpCAM in cancers: from bench to bedside.Experimental hematology & oncology · 2022Review
- Research Progress of DNA Methylation in Endometrial Cancer.Biomolecules · 2022Review
- Distinct promotor methylation at tumor suppressive genes in ovarian cancer stromal progenitor cells and ovarian cancer and its clinical implication.American journal of cancer research · 2022Article
- Tumor Promoting Effect of BMP Signaling in Endometrial Cancer.International journal of molecular sciences · 2021Article
- Functional Implications of the Dynamic Regulation of EpCAM during Epithelial-to-Mesenchymal Transition.Biomolecules · 2021Review
- Establishment and validation of a prognostic nomogram based on a novel five-DNA methylation signature for survival in endometrial cancer patients.Cancer medicine · 2021Article
- Identification of a Metabolism-Related Signature for the Prediction of Survival in Endometrial Cancer Patients.Frontiers in oncology · 2021Article
- Expression and function of epithelial cell adhesion molecule EpCAM: where are we after 40 years?Cancer metastasis reviews · 2020Review
- Genome-Wide DNA Methylation in Peripheral Blood and Long-Term Exposure to Source-Specific Transportation Noise and Air Pollution: The SAPALDIA Study.Environmental health perspectives · 2020Article
- Shedding light on the EpCAM: An overview.Journal of cellular physiology · 2019Review
- Article
- Ping-Pong-Tumor and Host in Pancreatic Cancer Progression.Frontiers in oncology · 2019Review
- miR-137 is a tumor suppressor in endometrial cancer and is repressed by DNA hypermethylation.Laboratory investigation; a journal of technical methods and pathology · 2018Article
- DNA methylation in lung tissues of mouse offspring exposed in utero to polycyclic aromatic hydrocarbons.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2017Article
- START: a system for flexible analysis of hundreds of genomic signal tracks in few lines of SQL-like queries.BMC genomics · 2017Article
- Mutual regulation of microRNAs and DNA methylation in human cancers.Epigenetics · 2017Review
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
purposeEpigenetic regulation by promoter methylation plays a key role in tumorigenesis. Our goal was to investigate whether altered DNA methylation signatures associated with oncogenic signaling delineate biomarkers predictive of endometrial cancer recurrence. EXPERIMENTAL
designMethyl-CpG-capture sequencing was used for global screening of aberrant DNA methylation in our endometrial cancer cohort, followed by validation in an independent The Cancer Genome Atlas (TCGA) cohort. Bioinformatics as well as functional analyses in vitro, using RNA interference (RNAi) knockdown, were performed to examine regulatory mechanisms of candidate gene expression and contribution to aggressive phenotype, such as epithelial-mesenchymal transition (EMT).
resultsWe identified 2,302 hypermethylated loci in endometrial tumors compared with control samples. Bone morphogenetic protein (BMP) family genes, including BMP1, 2, 3, 4, and 7, were among the frequently hypermethylated loci. Interestingly, BMP2, 3, 4, and 7 were less methylated in primary tumors with subsequent recurrence and in patients with shorter disease-free interval compared with nonrecurrent tumors, which was validated and associated with poor survival in the TCGA cohort (BMP4, P = 0.009; BMP7, P = 0.007). Stimulation of endometrial cancer cells with epidermal growth factor (EGF) induced EMT and transcriptional activation of these genes, which was mediated by the epithelial cell adhesion molecule (EpCAM). EGF signaling was implicated in maintaining the promoters of candidate BMP genes in an active chromatin configuration and thus subject to transcriptional activation.
conclusionsHypomethylation signatures of candidate BMP genes associated with EpCAM-mediated expression present putative biomarkers predictive of poor survival in endometrial cancer.
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