Evidence map›Paper›PMID 30926792›Full record

ArticleNature communications2019

Targeting bivalency de-represses Indian Hedgehog and inhibits self-renewal of colorectal cancer-initiating cells.

Evelyne Lima-Fernandes, Alex Murison, Tiago da Silva Medina, Yadong Wang, Anqi Ma, Cherry Leung, Genna M Luciani, Jennifer Haynes, Aaron Pollett, Constanze Zeller and 9 more

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

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
2.8field-weighted citation impact, top 8% 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

32 citing papers in PubMed, 49 citations in OpenAlex.

  1. Review
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  3. mNature communications · 2026
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  7. Epigenetic regulation of cancer stemness.Signal transduction and targeted therapy · 2025
    Review
  8. Mechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer.International journal of molecular sciences · 2025
    Review
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  17. Review
  18. Article
  19. Article
  20. Basophils as a potential therapeutic target in cancer.Journal of Zhejiang University. Science. B · 2021
    Review
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

19 authors at 4 institutions in 2 countries.

Evelyne Lima-FernandesStructural Genomics Consortium, University of Toronto, Toronto, ON, M5G1L7, Canada.ORCID http://orcid.org/0000-0002-3628-9745
Alex MurisonPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G1L7, Canada.
Tiago da Silva MedinaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G1L7, Canada.
Yadong WangPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G1L7, Canada.
Anqi MaMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences and Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Cherry LeungPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G1L7, Canada.
Genna M LucianiStructural Genomics Consortium, University of Toronto, Toronto, ON, M5G1L7, Canada.ORCID http://orcid.org/0000-0001-8107-2708
Jennifer HaynesPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G1L7, Canada.
Aaron PollettDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, M5S1A8, Canada.
Constanze ZellerPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G1L7, Canada.
Shili DuanDepartment of Medical Biophysics, University of Toronto, Toronto, ON, M5G1L7, Canada.
Antonija KresoPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G1L7, Canada.
Dalia Barsyte-LovejoyStructural Genomics Consortium, University of Toronto, Toronto, ON, M5G1L7, Canada.ORCID http://orcid.org/0000-0002-6560-9621
Bradly G WoutersPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G1L7, Canada.
Jian JinMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences and Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.ORCID http://orcid.org/0000-0002-2387-3862
Daniel D De CarvalhoPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G1L7, Canada.ORCID http://orcid.org/0000-0003-0771-2265
Mathieu LupienPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G1L7, Canada.ORCID http://orcid.org/0000-0003-0929-9478
Cheryl H ArrowsmithStructural Genomics Consortium, University of Toronto, Toronto, ON, M5G1L7, Canada. carrow@uhnresearch.ca.
Catherine A O'BrienPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G1L7, Canada. Catherine.OBrien@uhnresearch.ca.ORCID http://orcid.org/0000-0003-0682-3879
University Health Network · CAUniversity of Toronto · CAIcahn School of Medicine at Mount Sinai · USOntario Institute for Cancer Research · CA

Funding

Epigenetic Therapy and Prader-Willi SyndromeR01HD088626 · NICHD · YALE UNIVERSITY · PI JIANG, YONG-HUI, JIN, JIAN · 2017 to 2021
$2.8M
Targeting Lysine Methyltransferases EZH2 and EZH1 for Treating MLL-rearranged LeukemiasR01CA218600 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI JIN, JIAN, WANG, G GREG · 2017 to 2021
$2.8M
(PQ9) Developing EZH2 Degraders for Treating Triple-Negative Breast CancerR01CA230854 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI JIN, JIAN, PARSONS, RAMON E · 2018 to 2022
$1.5M
Discovery of Selective Inhibitors for Histone MethyltransferasesR01GM122749 · NIGMS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI JIN, JIAN · 2017 to 2020
$1.3M
NCI NIH HHS R01 CA218600NCI NIH HHS R01 CA230854NICHD NIH HHS R01 HD088626NIGMS NIH HHS R01 GM122749Wellcome Trust
6 · The paper itself

Abstract

In embryonic stem cells, promoters of key lineage-specific differentiation genes are found in a bivalent state, having both activating H3K4me3 and repressive H3K27me3 histone marks, making them poised for transcription upon loss of H3K27me3. Whether cancer-initiating cells (C-ICs) have similar epigenetic mechanisms that prevent lineage commitment is unknown. Here we show that colorectal C-ICs (CC-ICs) are maintained in a stem-like state through a bivalent epigenetic mechanism. Disruption of the bivalent state through inhibition of the H3K27 methyltransferase EZH2, resulted in decreased self-renewal of patient-derived C-ICs. Epigenomic analyses revealed that the promoter of Indian Hedgehog (IHH), a canonical driver of normal colonocyte differentiation, exists in a bivalent chromatin state. Inhibition of EZH2 resulted in de-repression of IHH, decreased self-renewal, and increased sensitivity to chemotherapy in vivo. Our results reveal an epigenetic block to differentiation in CC-ICs and demonstrate the potential for epigenetic differentiation therapy of a solid tumour through EZH2 inhibition.

Indexed as

Cell Self RenewalAnimalsBenzamidesCell DifferentiationCell ProliferationColorectal NeoplasmsEnhancer of Zeste Homolog 2 ProteinFemaleFluorouracilHedgehog ProteinsHumansIndazolesMaleMice, Inbred NODMice, SCIDNeoplastic Stem CellsBenzamidesEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanFluorouracilHedgehog ProteinsIHH protein, humanIndazolesPiperazinesPyridonesUNC1999

Identifiers

PMID30926792
PMCPMC6441108
OpenAlexW2926277490

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.