Evidence map›Paper›PMID 33979648›Full record

ArticleCell chemical biology2021

Targeting SUMOylation dependency in human cancer stem cells through a unique SAE2 motif revealed by chemical genomics.

Yannick D Benoit, Ryan R Mitchell, Wenliang Wang, Luca Orlando, Allison L Boyd, Borko Tanasijevic, Lili Aslostovar, Zoya Shapovalova, Meaghan Doyle, Christopher J Bergin and 17 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
–field-weighted citation impact
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

15 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. The PML hub: An emerging actor of leukemia therapies.The Journal of experimental medicine · 2023
    Article
  9. Review
  10. Article
  11. Signalling mechanisms and cellular functions of SUMO.Nature reviews. Molecular cell biology · 2022
    Review
  12. Article
  13. Protein sumoylation in normal and cancer stem cells.Frontiers in molecular biosciences · 2022
    Review
  14. Article
  15. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

27 authors.

Yannick D BenoitStem Cell and Cancer Research Institute, McMaster University, Hamilton, ON L8S 4K1, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Ryan R MitchellStem Cell and Cancer Research Institute, McMaster University, Hamilton, ON L8S 4K1, Canada.
Wenliang WangM.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton L8S 4K1, Canada.
Luca OrlandoDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada.
Allison L BoydDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada.
Borko TanasijevicStem Cell and Cancer Research Institute, McMaster University, Hamilton, ON L8S 4K1, Canada.
Lili AslostovarStem Cell and Cancer Research Institute, McMaster University, Hamilton, ON L8S 4K1, Canada.
Zoya ShapovalovaStem Cell and Cancer Research Institute, McMaster University, Hamilton, ON L8S 4K1, Canada.
Meaghan DoyleDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada.
Christopher J BerginDepartment of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Kinga VojnitsDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada.
Fanny L CasadoStem Cell and Cancer Research Institute, McMaster University, Hamilton, ON L8S 4K1, Canada.
Justin Di LuStem Cell and Cancer Research Institute, McMaster University, Hamilton, ON L8S 4K1, Canada.
Deanna P PorrasDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada.
Juan Luis García-RodriguezDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada.
Jennifer RussellStem Cell and Cancer Research Institute, McMaster University, Hamilton, ON L8S 4K1, Canada.
Aïcha ZouggarDepartment of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Angelique N MasibagDepartment of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Cody CabaM.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton L8S 4K1, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada.
Kalinka KotevaM.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton L8S 4K1, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada.
Lakshmana K KinthadaM.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton L8S 4K1, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada.
Jagdish Suresh PatelDepartment of Biological Sciences, Institute for Modeling Collaboration and Innovation, University of Idaho, Moscow, ID 83844, USA.
Sara N AndresM.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton L8S 4K1, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada.
Jakob MagolanM.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton L8S 4K1, Canada; Department of Chemistry and Chemical Biology, McMaster University, Hamilton, ON L8S 4K1, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada.
Tony J CollinsStem Cell and Cancer Research Institute, McMaster University, Hamilton, ON L8S 4K1, Canada.
Gerard D WrightM.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton L8S 4K1, Canada; Department of Chemistry and Chemical Biology, McMaster University, Hamilton, ON L8S 4K1, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada. Electronic address: wrightge@mcmaster.ca.
Mickie BhatiaStem Cell and Cancer Research Institute, McMaster University, Hamilton, ON L8S 4K1, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada. Electronic address: mbhatia@mcmaster.ca.

Funding

Sequence-structure-function relationships in human visual photopigmentsP20GM104420 · NIGMS · UNIVERSITY OF IDAHO · PI VAN LEUVEN, JAMES · 2015 to 2024
$22.9M
Genomics Resources Core (GRC)P30GM103324 · NIGMS · UNIVERSITY OF IDAHO · PI SETTLES, MATTHEW · 2013 to 2017
$5.0M
CIHR FRN 159925CIHR PJT- 173541NIGMS NIH HHS P20 GM104420NIGMS NIH HHS P30 GM103324
6 · The paper itself

Abstract

Natural products (NPs) encompass a rich source of bioactive chemical entities. Here, we used human cancer stem cells (CSCs) in a chemical genomics campaign with NP chemical space to interrogate extracts from diverse strains of actinomycete for anti-cancer properties. We identified a compound (McM25044) capable of selectively inhibiting human CSC function versus normal stem cell counterparts. Biochemical and molecular studies revealed that McM025044 exerts inhibition on human CSCs through the small ubiquitin-like modifier (SUMO) cascade, found to be hyperactive in a variety of human cancers. McM025044 impedes the SUMOylation pathway via direct targeting of the SAE1/2 complex. Treatment of patient-derived CSCs resulted in reduced levels of SUMOylated proteins and suppression of progenitor and stem cell capacity measured in vitro and in vivo. Our study overcomes a barrier in chemically inhibiting oncogenic SUMOylation activity and uncovers a unique role for SAE2 in the biology of human cancers.

Indexed as

AnimalsAntineoplastic AgentsBinding SitesBiological ProductsCell Line, TumorCell Self RenewalCell SurvivalHumansLeukemia, Myeloid, AcuteMiceMolecular Docking SimulationNeoplastic Stem CellsRNA InterferenceRNA, Small InterferingSumoylationUbiquitin-Activating EnzymesAntineoplastic AgentsBiological ProductsRNA, Small InterferingUBA2 protein, humanUbiquitin-Activating Enzymesdrugleukemianatural productsscreeningselectivitystem cellsSUMOylation

Identifiers

PMID33979648
PMCPMC8542640

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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.