ArticleCancer cell2019
Aging-like Spontaneous Epigenetic Silencing Facilitates Wnt Activation, Stemness, and Braf
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Article in Cancer cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 1 of them a synthesis that pooled it.
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115citing papers in PubMed, 1 pooled it
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Who cites it
115 citing papers in PubMed, 1 synthesis or guideline pooled it, 189 citations in OpenAlex.
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- Epigenetic reprogramming in multiple myeloma-Challenges and opportunities.International journal of cancer · 2026Review
- Organoid: a promising solution to current challenges in cancer immunotherapy.npj biomedical innovations · 2025Review
- Iron homeostasis and cell clonality drive cancer-associated intestinal DNA methylation drift in aging.Nature aging · 2025Article
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- Unravelling the genetics and epigenetics of the ageing tumour microenvironment in cancer.Nature reviews. Cancer · 2025Review
- Genome-wide profiling of unmodified DNA using methyltransferase-directed tagging and enrichment.Cell reports methods · 2025Article
- Modelling the ageing dependence of cancer evolutionary trajectories.Nature reviews. Cancer · 2025Review
- Aging-Related Mechanisms Underlying Carcinogenesis: Therapeutic Opportunities.Aging and disease · 2025Review
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- Colonic Aging and Colorectal Cancer: An Unignorable Interplay and Its Translational Implications.Biology · 2025Review
- Unveiling the Relation between Cellular Aging, Epigenetics and Cancer.Aging and disease · 2025Article
- Comprehensive metabolomic and epigenomic characterization of microsatellite stable BRAF-mutated colorectal cancer.Oncogene · 2025Article
- Simulation-guided pan-cancer analysis identifies a novel regulator of CpG island hypermethylation heterogeneity.Briefings in bioinformatics · 2025Article
55 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 9 institutions in 4 countries.
Yong TaoCRB1, Department of Oncology and The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Room 530, Baltimore, MD 21287, USA.
Byunghak KangCRB1, Department of Oncology and The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Room 530, Baltimore, MD 21287, USA.
Daniel A PetkovichCRB1, Department of Oncology and The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Room 530, Baltimore, MD 21287, USA.
Yuba R BhandariCRB1, Department of Oncology and The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Room 530, Baltimore, MD 21287, USA.
Julie InHopkins Conte Digestive Disease, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Genevieve Stein-O'BrienDivision of Biostatistics & Bioinformatics, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Xiangqian KongCRB1, Department of Oncology and The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Room 530, Baltimore, MD 21287, USA.
Wenbing XieCRB1, Department of Oncology and The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Room 530, Baltimore, MD 21287, USA.
Nicholas ZachosHopkins Conte Digestive Disease, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Shinji MaegawaDepartment of Pediatrics, University of Texas, MD Anderson Cancer Center, Unit 853, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Himani VaidyaFels Institute for Cancer Research and Molecular Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19122, USA.
Stephen BrownCRB1, Department of Oncology and The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Room 530, Baltimore, MD 21287, USA.
Ray-Whay Chiu YenCRB1, Department of Oncology and The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Room 530, Baltimore, MD 21287, USA.
Xiaojian ShaoDepartment of Human Genetics, Canadian Centre for Computational Genomics, McGill University, Montreal, QC, Canada.
Jai ThakorCRB1, Department of Oncology and The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Room 530, Baltimore, MD 21287, USA.
Zhihao LuDepartment of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, China.
Yi CaiCRB1, Department of Oncology and The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Room 530, Baltimore, MD 21287, USA.
Yuezheng ZhangDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Izaskun MallonaGermans Trias i Pujol Health Science Research Institute (IGTP), Program for Personalized Medicine of Cancer, Badalona, 08916 Catalonia, Spain.
Miguel Angel PeinadoGermans Trias i Pujol Health Science Research Institute (IGTP), Program for Personalized Medicine of Cancer, Badalona, 08916 Catalonia, Spain.
Cynthia A ZahnowCRB1, Department of Oncology and The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Room 530, Baltimore, MD 21287, USA.
Nita AhujaCRB1, Department of Oncology and The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Room 530, Baltimore, MD 21287, USA.
Elana FertigDivision of Biostatistics & Bioinformatics, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Jean-Pierre IssaFels Institute for Cancer Research and Molecular Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19122, USA.
Stephen B BaylinCRB1, Department of Oncology and The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Room 530, Baltimore, MD 21287, USA. Electronic address: sbaylin1@jhmi.edu.
Hariharan EaswaranCRB1, Department of Oncology and The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Room 530, Baltimore, MD 21287, USA. Electronic address: heaswar1@jhmi.edu.
Johns Hopkins University · USSidney Kimmel Comprehensive Cancer Center · USInstitute of Predictive and Personalized Medicine of Cancer · ESJohns Hopkins Medicine · USTemple University · USMcGill University · CAPeking University Cancer Hospital · CNThe University of Texas MD Anderson Cancer Center · USUniversity of Washington · US
Funding
Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI WILLIAM George NELSON · 1985 to 2026
$208.6MTumor Antigens for Individual Signatures and TherapyP50CA062924 · NCI · JOHNS HOPKINS UNIVERSITY · PI JAFFEE, ELIZABETH M. · 1993 to 2022
$54.6MBIOCHEMISTRY, CELLULAR AND MOLECULAR BIOLOGY PROGRAMT32GM007445 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI GREEN, RACHEL · 1985 to 2021
$24.1MTranslational Research Enhancement CoreP30DK089502 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI ZACHOS, NICHOLAS CONSTANTINE · 2011 to 2020
$12.0MDNA Methyltrasferase Gene Expression in Colon CancerR01ES011858 · NIEHS · JOHNS HOPKINS UNIVERSITY · PI BAYLIN, STEPHEN B., EASWARAN, HARIHARAN · 2002 to 2023
$11.5MEpigenetic Drivers of Cancer (PQ 10)R01CA170550 · NCI · VAN ANDEL RESEARCH INSTITUTE · PI BAYLIN, STEPHEN B., JONES, PETER A · 2012 to 2015
$2.4M(PQ4) - Tools for simultaneous disruption of multiple epigenetically silenced genes for studying their roles in tumorigenesis using ex vivo human and mouse colon organoid and in vivo mouse modelsR01CA230995 · NCI · JOHNS HOPKINS UNIVERSITY · PI BAYLIN, STEPHEN B., EASWARAN, HARIHARAN · 2018 to 2022
$1.9M(PQD3)Molecular Profiles associated with Long-Term Survival in pancreas CancerR01CA185357 · NCI · YALE UNIVERSITY · PI AHUJA, NITA · 2014 to 2017
$1.8MHigh-efficiency microfluidic-assisted single-cell DNA methylome sequencingR21CA212495 · NCI · JOHNS HOPKINS UNIVERSITY · PI EASWARAN, HARIHARAN, PISANIC II, THOMAS RUSSELL · 2017 to 2019
$729kHuman Enteroids as a Model of Host-EHEC InteractionsK01DK106323 · NIDDK · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI IN, JULIE GOEUN · 2016 to 2020
$711kNCI NIH HHS P30 CA006973NCI NIH HHS P50 CA062924NCI NIH HHS R01 CA170550NCI NIH HHS R01 CA185357NCI NIH HHS R01 CA230995NCI NIH HHS R21 CA212495NIDDK NIH HHS K01 DK106323NIDDK NIH HHS P30 DK089502NIEHS NIH HHS R01 ES011858NIGMS NIH HHS T32 GM007445
Abstract
We addressed the precursor role of aging-like spontaneous promoter DNA hypermethylation in initiating tumorigenesis. Using mouse colon-derived organoids, we show that promoter hypermethylation spontaneously arises in cells mimicking the human aging-like phenotype. The silenced genes activate the Wnt pathway, causing a stem-like state and differentiation defects. These changes render aged organoids profoundly more sensitive than young ones to transformation by Braf
Indexed as
DNA MethylationGene SilencingMutationAdenocarcinomaAge FactorsAgingAnimalsCell Transformation, NeoplasticColonic NeoplasmsGene Expression Regulation, NeoplasticGenetic Predisposition to DiseaseHumansMice, Inbred NODMice, Mutant StrainsMice, SCIDPhenotypeBRAF protein, humanBraf protein, mouseProto-Oncogene Proteins B-rafagingBRAF(V600E)cancer riskCIMPcolon adenocarcinomasCpG-island DNA methylationepigenetic silencingtransformationtumorigenesistumor predisposition
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