Evidence map›Paper›PMID 34784298›Full record

ArticleJCI insight2021

Intestinal epithelial glucocorticoid receptor promotes chronic inflammation-associated colorectal cancer.

Shuang Tang, Zhan Zhang, Robert H Oakley, Wenling Li, Weijing He, Xiaojiang Xu, Ming Ji, Qing Xu, Liang Chen, Alicia S Wellman and 6 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.2field-weighted citation impact, top 9% 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

13 citing papers in PubMed, 27 citations in OpenAlex.

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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

16 authors at 3 institutions in 2 countries.

Shuang TangSignal Transduction Laboratory, National Institute of Environmental Health Sciences, NIH, Durham, North Carolina, USA.
Zhan ZhangSignal Transduction Laboratory, National Institute of Environmental Health Sciences, NIH, Durham, North Carolina, USA.
Robert H OakleySignal Transduction Laboratory, National Institute of Environmental Health Sciences, NIH, Durham, North Carolina, USA.
Wenling LiBiostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, NIH, Durham, North Carolina, USA.
Weijing HeDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Xiaojiang XuIntegrative Bioinformatics Group, National Institute of Environmental Health Sciences, NIH, Durham, North Carolina, USA.
Ming JiSignal Transduction Laboratory, National Institute of Environmental Health Sciences, NIH, Durham, North Carolina, USA.
Qing XuSignal Transduction Laboratory, National Institute of Environmental Health Sciences, NIH, Durham, North Carolina, USA.
Liang ChenSignal Transduction Laboratory, National Institute of Environmental Health Sciences, NIH, Durham, North Carolina, USA.
Alicia S WellmanSignal Transduction Laboratory, National Institute of Environmental Health Sciences, NIH, Durham, North Carolina, USA.
Qingguo LiDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Leping LiBiostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, NIH, Durham, North Carolina, USA.
Jian-Liang LiIntegrative Bioinformatics Group, National Institute of Environmental Health Sciences, NIH, Durham, North Carolina, USA.
Xinxiang LiDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
John A CidlowskiSignal Transduction Laboratory, National Institute of Environmental Health Sciences, NIH, Durham, North Carolina, USA.
Xiaoling LiSignal Transduction Laboratory, National Institute of Environmental Health Sciences, NIH, Durham, North Carolina, USA.
National Institute of Environmental Health Sciences · USFudan University Shanghai Cancer Center · CNWuhan University · CN

Funding

Sirtuins and nuclear receptors in aging and age-associated diseasesZIAES102205 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI LI, XIAOLING · 2009 to 2025
$42.4M
Intramural NIH HHS ZIA ES102205
6 · The paper itself

Abstract

Synthetic immunosuppressive glucocorticoids (GCs) are widely used to control inflammatory bowel disease (IBD). However, the impact of GC signaling on intestinal tumorigenesis remains controversial. Here, we report that intestinal epithelial GC receptor (GR), but not whole intestinal tissue GR, promoted chronic intestinal inflammation-associated colorectal cancer in both humans and mice. In patients with colorectal cancer, GR was enriched in intestinal epithelial cells and high epithelial cell GR levels were associated with poor prognosis. Consistently, intestinal epithelium-specific deletion of GR (GR iKO) in mice increased macrophage infiltration, improved tissue recovery, and enhanced antitumor response in a chronic inflammation-associated colorectal cancer model. Consequently, GR iKO mice developed fewer and less advanced tumors than control mice. Furthermore, oral GC administration in the early phase of tissue injury delayed recovery and accelerated the formation of aggressive colorectal cancers. Our study reveals that intestinal epithelial GR signaling repressed acute colitis but promoted chronic inflammation-associated colorectal cancer. Our study suggests that colorectal epithelial GR could serve as a predictive marker for colorectal cancer risk and prognosis. Our findings further suggest that, although synthetic GC treatment for IBD should be used with caution, there is a therapeutic window for GC therapy during colorectal cancer development in immunocompetent patients.

Indexed as

AnimalsChronic DiseaseColorectal NeoplasmsDisease Models, AnimalHumansInflammationIntestinesMaleMiceReceptors, GlucocorticoidReceptors, GlucocorticoidColorectal cancerGastroenterologyInflammatory bowel diseaseInnate immunityOncology

Identifiers

PMID34784298
PMCPMC8783679
OpenAlexW3213598026

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.