Evidence map›Paper›PMID 25908435›Full record

ArticleNature communications2015

DNMT1 is essential for mammary and cancer stem cell maintenance and tumorigenesis.

Rajneesh Pathania, Sabarish Ramachandran, Selvakumar Elangovan, Ravi Padia, Pengyi Yang, Senthilkumar Cinghu, Rajalakshmi Veeranan-Karmegam, Pachiappan Arjunan, Jaya P Gnana-Prakasam, Fulzele Sadanand and 10 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 148 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
148citing papers in PubMed, 2 pooled it
12.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

148 citing papers in PubMed, 2 syntheses or guidelines pooled it, 257 citations in OpenAlex.

  1. Pooled it
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  14. Epigenetic regulation of cancer stemness.Signal transduction and targeted therapy · 2025
    Review
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  17. Article
  18. Article
  19. New insights on anti-tumor immunity of CD8Journal of translational medicine · 2025
    Review
  20. Article

88 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors at 2 institutions in 1 country.

Rajneesh PathaniaDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912, USA.
Sabarish RamachandranDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912, USA.
Selvakumar ElangovanDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912, USA.
Ravi PadiaDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912, USA.
Pengyi YangSystem Biology Section, Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
Senthilkumar CinghuSystem Biology Section, Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
Rajalakshmi Veeranan-KarmegamDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912, USA.
Pachiappan ArjunanDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912, USA.
Jaya P Gnana-PrakasamDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912, USA.
Fulzele SadanandDepartment of Orthopedic Surgery, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912, USA.
Lirong PeiDepartment of Pathology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912, USA.
Chang-Sheng ChangDepartment of Pathology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912, USA.
Jeong-Hyeon ChoiDepartment of Biostatistics, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912, USA.
Huidong ShiDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912, USA.
Santhakumar ManicassamyCancer Research Center, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912, USA.
Puttur D PrasadDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912, USA.
Suash SharmaDepartment of Pathology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912, USA.
Vadivel GanapathyDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912, USA.
Raja JothiSystem Biology Section, Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
Muthusamy ThangarajuDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912, USA.
Augusta University · USNational Institutes of Health · US

Funding

Gene regulatory elements, networks, and mechanismsZIAES102625 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI JOTHI, RAJA · 2009 to 2025
$27.4M
Regulation of Oral Tolerance and Intestinal Inflammation by Beta-catenin/TCF PathR01DK097271 · NIDDK · AUGUSTA UNIVERSITY · PI MANICASSAMY, SANTHAKUMAR · 2012 to 2016
$1.6M
Tumor-Suppressive Function of SLC5A8 in Mammary Gland and its Relevance to BreastR01CA131402 · NCI · AUGUSTA UNIVERSITY · PI THANGARAJU, MUTHUSAMY · 2008 to 2012
$1.3M
Programming dendritic cells to induce tolerogenic response and suppress brain infR56AI104875 · NIAID · AUGUSTA UNIVERSITY · PI MANICASSAMY, SANTHAKUMAR · 2013 to 2013
$353k
Intramural NIH HHS ZIA ES102625NCI NIH HHS CA131402NCI NIH HHS R01 CA131402NIAID NIH HHS R56 AI104875NIDDK NIH HHS R01 DK097271PHS HHS 1ZIAES102625
6 · The paper itself

Abstract

Mammary stem/progenitor cells (MaSCs) maintain self-renewal of the mammary epithelium during puberty and pregnancy. DNA methylation provides a potential epigenetic mechanism for maintaining cellular memory during self-renewal. Although DNA methyltransferases (DNMTs) are dispensable for embryonic stem cell maintenance, their role in maintaining MaSCs and cancer stem cells (CSCs) in constantly replenishing mammary epithelium is unclear. Here we show that DNMT1 is indispensable for MaSC maintenance. Furthermore, we find that DNMT1 expression is elevated in mammary tumours, and mammary gland-specific DNMT1 deletion protects mice from mammary tumorigenesis by limiting the CSC pool. Through genome-scale methylation studies, we identify ISL1 as a direct DNMT1 target, hypermethylated and downregulated in mammary tumours and CSCs. DNMT inhibition or ISL1 expression in breast cancer cells limits CSC population. Altogether, our studies uncover an essential role for DNMT1 in MaSC and CSC maintenance and identify DNMT1-ISL1 axis as a potential therapeutic target for breast cancer treatment.

Indexed as

AnimalsBlotting, WesternBreast NeoplasmsCarcinogenesisCell LineCell Line, TumorDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA MethylationDown-RegulationFemaleHumansLIM-Homeodomain ProteinsMammary Glands, AnimalMammary Neoplasms, ExperimentalMCF-7 CellsDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNMT1 protein, humanDnmt1 protein, mouseinsulin gene enhancer binding protein Isl-1LIM-Homeodomain ProteinsTranscription Factors

Identifiers

PMID25908435
PMCPMC4410389
OpenAlexW2075214050

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.