Evidence map›Paper›PMID 32709883›Full record

ArticleNature communications2020

Copper bioavailability is a KRAS-specific vulnerability in colorectal cancer.

Léo Aubert, Neethi Nandagopal, Zachary Steinhart, Geneviève Lavoie, Sami Nourreddine, Jacob Berman, Marc K Saba-El-Leil, David Papadopoli, Sichun Lin, Traver Hart and 8 more

Abstract read
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
153citing papers in PubMed, 2 pooled it
–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

153 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Article
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  7. Review
  8. Review
  9. Article
  10. A broad-spectrum inhibitor of copper-exporting PProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  11. Article
  12. Article
  13. Article
  14. Review
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  19. A First-In-Class Broad Spectrum Inhibitor of Copper Exporting PbioRxiv : the preprint server for biology · 2026
    Article
  20. Article

93 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

18 authors.

Léo Aubert *Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, 2950, Chemin de la Polytechnique, Montréal, QC, H3T 1J4, Canada.
Neethi Nandagopal *Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, 2950, Chemin de la Polytechnique, Montréal, QC, H3T 1J4, Canada.
Zachary SteinhartDepartment of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, ON, M5S 3M2, Canada.
Geneviève LavoieInstitute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, 2950, Chemin de la Polytechnique, Montréal, QC, H3T 1J4, Canada.
Sami NourreddineInstitute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, 2950, Chemin de la Polytechnique, Montréal, QC, H3T 1J4, Canada.
Jacob BermanLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, 600 University Ave., Toronto, ON, M5G 1X5, Canada.
Marc K Saba-El-LeilInstitute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, 2950, Chemin de la Polytechnique, Montréal, QC, H3T 1J4, Canada.
David PapadopoliDepartment of Oncology, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, 3755 Côte Sainte-Catherine Road, Montreal, QC, H3T 1E2, Canada.
Sichun LinDepartment of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, ON, M5S 3M2, Canada.
Traver HartMD Anderson Cancer Center, University of Texas, 515 Holcombe Blvd, Houston, TX, 77030, USA.
Graham MacleodDepartment of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, ON, M5S 3M2, Canada.ORCID http://orcid.org/0000-0001-6401-9307
Ivan TopisirovicDepartment of Oncology, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, 3755 Côte Sainte-Catherine Road, Montreal, QC, H3T 1E2, Canada.ORCID http://orcid.org/0000-0002-5510-9762
Louis GabouryInstitute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, 2950, Chemin de la Polytechnique, Montréal, QC, H3T 1J4, Canada.
Christoph J FahrniSchool of Chemistry and Biochemistry, Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Dr NW, Atlanta, GA, 30332, USA.ORCID http://orcid.org/0000-0003-3731-7434
Daniel SchramekLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, 600 University Ave., Toronto, ON, M5G 1X5, Canada.ORCID http://orcid.org/0000-0001-9977-2104
Sylvain MelocheInstitute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, 2950, Chemin de la Polytechnique, Montréal, QC, H3T 1J4, Canada.ORCID http://orcid.org/0000-0002-6201-7786
Stephane AngersDepartment of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, ON, M5S 3M2, Canada.ORCID http://orcid.org/0000-0001-7241-9044
Philippe P RouxInstitute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, 2950, Chemin de la Polytechnique, Montréal, QC, H3T 1J4, Canada. philippe.roux@umontreal.ca.ORCID http://orcid.org/0000-0002-5962-0250

Funding

Molecular Tools to Illuminate Copper Transport and HomeostasisR01GM067169 · NIGMS · GEORGIA INSTITUTE OF TECHNOLOGY · PI FAHRNI, CHRISTOPH J · 2004 to 2018
$3.5M
Molecular Tools to Illuminate Copper Transport and HomeostasisR35GM136404 · NIGMS · GEORGIA INSTITUTE OF TECHNOLOGY · PI FAHRNI, CHRISTOPH J · 2020 to 2024
$2.2M
CIHR MOP-142374CIHR PJT-152995NIGMS NIH HHS R01 GM067169NIGMS NIH HHS R35 GM136404
6 · The paper itself

Abstract

Despite its importance in human cancers, including colorectal cancers (CRC), oncogenic KRAS has been extremely challenging to target therapeutically. To identify potential vulnerabilities in KRAS-mutated CRC, we characterize the impact of oncogenic KRAS on the cell surface of intestinal epithelial cells. Here we show that oncogenic KRAS alters the expression of a myriad of cell-surface proteins implicated in diverse biological functions, and identify many potential surface-accessible therapeutic targets. Cell surface-based loss-of-function screens reveal that ATP7A, a copper-exporter upregulated by mutant KRAS, is essential for neoplastic growth. ATP7A is upregulated at the surface of KRAS-mutated CRC, and protects cells from excess copper-ion toxicity. We find that KRAS-mutated cells acquire copper via a non-canonical mechanism involving macropinocytosis, which appears to be required to support their growth. Together, these results indicate that copper bioavailability is a KRAS-selective vulnerability that could be exploited for the treatment of KRAS-mutated neoplasms.

Indexed as

AnimalsBiological AvailabilityCell Line, TumorCell ProliferationColorectal NeoplasmsCopperCopper-Transporting ATPasesCRISPR-Cas SystemsFemaleHumansIntestinal MucosaMiceMice, KnockoutMice, NudeMice, SCIDMutationATP7A protein, humanCopperCopper-Transporting ATPasesKRAS protein, humanProto-Oncogene Proteins p21(ras)

Identifiers

PMID32709883
PMCPMC7381612

What OpenQuestion holds

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Registered trials

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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.