Evidence map›Paper›PMID 30885780›Full record

ArticleGastroenterology2019

PPARD and Interferon Gamma Promote Transformation of Gastric Progenitor Cells and Tumorigenesis in Mice.

Xiangsheng Zuo, Yasunori Deguchi, Weiguo Xu, Yi Liu, Haiyan S Li, Daoyan Wei, Rui Tian, Weidong Chen, Min Xu, Yaying Yang and 15 more

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

Article in Gastroenterology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
3.2field-weighted citation impact, top 7% 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

30 citing papers in PubMed, 62 citations in OpenAlex.

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  19. Identifying the Metabolic Signatures of PPARD-Overexpressing Gastric Tumors.International journal of molecular sciences · 2022
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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

25 authors at 2 institutions in 1 country.

Xiangsheng ZuoDepartments of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: xzuo@mdanderson.org.
Yasunori DeguchiDepartments of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Weiguo XuDepartments of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Yi LiuDepartments of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Haiyan S LiDepartments of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Daoyan WeiDepartments of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Rui TianDepartments of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Weidong ChenDepartments of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Min XuDepartments of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Yaying YangDepartments of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Shen GaoDepartments of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Jonathan C JaoudeDepartments of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Fuyao LiuDepartments of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Sarah P ChriekiDepartments of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Micheline J MoussalliDepartments of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Mihai GageaDepartments of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Manu M SebastianDepartments of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Xiaofeng ZhengDepartments of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Dongfeng TanDepartments of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Russell BroaddusDepartments of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Jing WangDepartments of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Nadim J AjamiAlkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, Texas; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas.
Alton G SwennesDepartment of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas; Center for Comparative Medicine, Baylor College of Medicine, Houston, Texas.
Stephanie S WatowichDepartments of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Imad ShureiqiDepartments of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: ishureiqi@mdanderson.org.
The University of Texas MD Anderson Cancer Center · USBaylor College of Medicine · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
Tissue Analysis & Molecular Imaging CoreP30DK056338 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI James Versalovic · 2001 to 2026
$28.3M
15-LOX-1 Regulation of Resolving Generation to Modulate Colon CancerR01CA195686 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI SHUREIQI, IMAD · 2016 to 2020
$1.8M
15-LOX-1 Modulation of Colon Cancer Promotion by Linoleic AcidR01CA206539 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI SHUREIQI, IMAD · 2016 to 2020
$1.8M
Molecular targeting of PPAR-delta in colon cancerR01CA142969 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI SHUREIQI, IMAD · 2010 to 2014
$1.6M
NCI NIH HHS P30 CA016672NCI NIH HHS R01 CA142969NCI NIH HHS R01 CA195686NCI NIH HHS R01 CA206539NIDDK NIH HHS P30 DK056338
6 · The paper itself

Abstract

BACKGROUND &

aimsThe peroxisome proliferator-activated receptor delta (PPARD) regulates cell metabolism, proliferation, and inflammation and has been associated with gastric and other cancers. Villin-positive epithelial cells are a small population of quiescent gastric progenitor cells. We expressed PPARD from a villin promoter to investigate the role of these cells and PPARD in development of gastric cancer.

methodsWe analyzed gastric tissues from mice that express the Ppard (PPARD1 and PPARD2 mice) from a villin promoter, and mice that did not carry this transgene (controls), by histology and immunohistochemistry. We performed cell lineage-tracing experiments and analyzed the microbiomes, chemokine and cytokine production, and immune cells and transcriptomes of stomachs of these mice. We also performed immunohistochemical analysis of PPARD levels in 2 sets of human gastric tissue microarrays.

resultsThirty-eight percent of PPARD mice developed spontaneous, invasive gastric adenocarcinomas, with severe chronic inflammation. Levels of PPARD were increased in human gastric cancer tissues, compared with nontumor tissues, and associated with gastric cancer stage and grade. We found an inverse correlation between level of PPARD in tumor tissue and patient survival time. Gastric microbiomes from PPARD and control mice did not differ significantly. Lineage-tracing experiments identified villin-expressing gastric progenitor cells (VGPCs) as the origin of gastric tumors in PPARD mice. In these mice, PPARD up-regulated CCL20 and CXCL1, which increased infiltration of the gastric mucosa by immune cells. Immune cell production of inflammatory cytokines promoted chronic gastric inflammation and expansion and transformation of VGPCs, leading to tumorigenesis. We identified a positive-feedback loop between PPARD and interferon gamma signaling that sustained gastric inflammation to induce VGPC transformation and gastric carcinogenesis.

conclusionsWe found PPARD overexpression in VPGCs to result in inflammation, dysplasia, and tumor formation. PPARD and VGPCs might be therapeutic targets for stomach cancer.

Indexed as

AdenocarcinomaAnimalsCarcinogenesisCell LineageCell Transformation, NeoplasticChemokine CCL20Chemokine CXCL1ChemokinesCytokinesFeedback, PhysiologicalGastric MucosaGene Expression ProfilingInflammationInterferon-gammaMiceMicrobiotaCCL20 protein, mouseChemokine CCL20Chemokine CXCL1ChemokinesCxcl1 protein, mouseCytokinesInterferon-gammaMicrofilament ProteinsPpard protein, mouseReceptors, Cytoplasmic and NuclearVil1 protein, mouseIFNGMouse ModelNuclear FactorTumor Stem Cell

Identifiers

PMID30885780
PMCPMC6581611
OpenAlexW2921015573

What OpenQuestion holds

Textmetadata
LicenceTDM
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.