Evidence map›Paper›PMID 32060280›Full record

ArticleNature communications2020

Inflammation mobilizes copper metabolism to promote colon tumorigenesis via an IL-17-STEAP4-XIAP axis.

Yun Liao, Junjie Zhao, Katarzyna Bulek, Fangqiang Tang, Xing Chen, Gang Cai, Shang Jia, Paul L Fox, Emina Huang, Theresa T Pizarro and 7 more

Open access · goldAbstract 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 122 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
122citing papers in PubMed, 1 pooled it
13.5field-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

122 citing papers in PubMed, 1 synthesis or guideline pooled it, 237 citations in OpenAlex.

  1. Pooled it
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  13. Disruption of NF-κB-Mediated Copper Homeostasis Sensitizes Breast Cancer to Cuproptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
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  18. Copper Homeostasis, Emerging Central Players in Cancer Immunotherapy.Journal of cellular and molecular medicine · 2025
    Review
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  20. Article

62 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

17 authors at 6 institutions in 3 countries.

Yun Liao *Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Junjie Zhao *Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Katarzyna BulekDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Fangqiang TangDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Xing ChenDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Gang CaiDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Shang JiaDepartments of Chemistry and Molecular and Cell Biology, University of California, Berkeley, CA, 94720, USA.ORCID http://orcid.org/0000-0001-6285-8959
Paul L FoxDepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Emina HuangDepartment of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.ORCID http://orcid.org/0000-0003-2495-4370
Theresa T PizarroDepartment of Pathology, Case Western Reserve University, Cleveland, OH, 44106, USA.
Matthew F KaladyDepartment of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Mark W JacksonDepartment of Pathology, Case Western Reserve University, Cleveland, OH, 44106, USA.
Shideng BaoDepartment of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Ganes C SenDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
George R StarkDepartment of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Christopher J ChangDepartments of Chemistry and Molecular and Cell Biology, University of California, Berkeley, CA, 94720, USA.
Xiaoxia LiDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA. lix@ccf.org.ORCID http://orcid.org/0000-0002-4872-9525
Cleveland Clinic Lerner College of Medicine · USCase Western Reserve University · USHoward Hughes Medical Institute · USJagiellonian University · PLSichuan University · CNUniversity of California, Berkeley · US

Funding

TELOMERASE INACTIVATION BY RNASE L SIGNALS CELL DEATHP01CA062220 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI LI, XIAOXIA, STARK, GEORGE ROBERT · 1994 to 2020
$35.6M
Targeting pathological hyaluronan matricesP01HL103453 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI ERZURUM, SERPIL C. · 2011 to 2020
$26.8M
The Cleveland Digestive Diseases Research Core Center (DDRCC)P30DK097948 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI AMITABH CHAK · 2015 to 2026
$15.6M
Molecular Imaging Probes To Study Redox BiologyR01GM079465 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI Christopher J. Chang · 2006 to 2026
$7.8M
An organotypic model recapitulating colon cancer microenvironment and metastasisU01CA214300 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI HUANG, EMINA HUI-NA, SHEN, XILING · 2017 to 2021
$3.1M
Microenvironment Interleukin-17 and Colorectal Cancer Treatment ResistanceR01CA193359 · NCI · OHIO STATE UNIVERSITY · PI KALADY, MATTHEW FRANK · 2015 to 2019
$1.8M
Leica TCS SP8 Confocal Microscope for a Core FacilityS10OD019972 · OD · CLEVELAND CLINIC LERNER COM-CWRU · PI DRAZBA, JUDY · 2015 to 2015
$544k
NCI NIH HHS P01 CA062220NCI NIH HHS R01 CA193359NCI NIH HHS U01 CA214300NHLBI NIH HHS P01 HL103453NIDDK NIH HHS P30 DK097948NIGMS NIH HHS R01 GM079465NIH HHS S10 OD019972
6 · The paper itself

Abstract

Copper levels are known to be elevated in inflamed and malignant tissues. But the mechanism underlying this selective enrichment has been elusive. In this study, we report a axis by which inflammatory cytokines, such as IL-17, drive cellular copper uptake via the induction of a metalloreductase, STEAP4. IL-17-induced elevated intracellular copper level leads to the activation of an E3-ligase, XIAP, which potentiates IL-17-induced NFκB activation and suppresses the caspase 3 activity. Importantly, this IL-17-induced STEAP4-dependent cellular copper uptake is critical for colon tumor formation in a murine model of colitis-associated tumorigenesis and STEAP4 expression correlates with IL-17 level and XIAP activation in human colon cancer. In summary, this study reveals a IL-17-STEAP4-XIAP axis through which the inflammatory response induces copper uptake, promoting colon tumorigenesis.

Indexed as

AnimalsCarcinogenesisColitisColonColonic NeoplasmsCopperHumansInhibitor of Apoptosis ProteinsInterleukin-17Membrane ProteinsMiceMice, Inbred C57BLMice, KnockoutBirc4 protein, mouseCopperInhibitor of Apoptosis ProteinsInterleukin-17Membrane ProteinsTiarp protein, mouse

Identifiers

PMID32060280
PMCPMC7021685
OpenAlexW3005771431

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.