Evidence map›Paper›PMID 31315643›Full record

ArticleJournal of experimental & clinical cancer research : CR2019

A positive feedback between IDO1 metabolite and COL12A1 via MAPK pathway to promote gastric cancer metastasis.

Zhen Xiang, Jun Li, Shuzheng Song, Jiexuan Wang, Wei Cai, Wenjun Hu, Jun Ji, Zhenggang Zhu, Lu Zang, Ranlin Yan and 1 more

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

Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed, 1 pooled it
4.2field-weighted citation impact, top 5% 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

82 citing papers in PubMed, 1 synthesis or guideline pooled it, 142 citations in OpenAlex.

  1. Pooled it
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  4. Association of IL4I1Frontiers in immunology · 2026
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22 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

11 authors at 2 institutions in 1 country.

Zhen XiangDepartment of Surgery of Ruijin Hospital, and Shanghai Key Laboratory for Gastric Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jun LiDepartment of Surgery of Ruijin Hospital, and Shanghai Key Laboratory for Gastric Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shuzheng SongDepartment of Surgery of Ruijin Hospital, and Shanghai Key Laboratory for Gastric Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jiexuan WangDepartment of Surgery of Ruijin Hospital, and Shanghai Key Laboratory for Gastric Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Wei CaiDepartment of Surgery of Ruijin Hospital, and Shanghai Key Laboratory for Gastric Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Wenjun HuDepartment of Surgery of Ruijin Hospital, and Shanghai Key Laboratory for Gastric Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jun JiDepartment of Surgery of Ruijin Hospital, and Shanghai Key Laboratory for Gastric Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Zhenggang ZhuDepartment of Surgery of Ruijin Hospital, and Shanghai Key Laboratory for Gastric Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Lu ZangDepartment of Surgery of Ruijin Hospital, and Shanghai Key Laboratory for Gastric Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ranlin YanDepartment of Surgery of Ruijin Hospital, and Shanghai Key Laboratory for Gastric Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yingyan YuDepartment of Surgery of Ruijin Hospital, and Shanghai Key Laboratory for Gastric Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, China. yingyan3y@sjtu.edu.cn.
Shanghai Jiao Tong University · CNRuijin Hospital · CN

Funding

National Natural Science Foundation of China 81372644National Natural Science Foundation of China 81772505
6 · The paper itself

Abstract

backgroundIDO1 (Indoleamine 2,3-dioxygenase 1) inhibits host anti-tumor immune response by exhausting tryptophan in tumor microenvironment, but the pathogenic mechanisms of IDO1 in gastric cancer (GC) cells need to be further explored.

methodsThe aim of this study was to use CCLE (Cancer Cell Line Encyclopedia) transcriptomic data of GC cell lines for WGCNA (Weighted Gene Co-expression Network Analysis) analysis, and explore the potential functions and mechanisms of IDO1 in GC progression in vitro and in vivo.

resultsThe higher expression level of IDO1 was identified in 4 out of 7 GC cell lines. Increased IDO1 expression strongly promoted cell migration via its metabolite kynurenine and was associated with pathways of immune activation according to GSEA (Gene Set Enrichment Analysis). The functions of IDO1 were closely associated with extracellular matrix, collagen metabolic and catabolic process by WGCNA analysis. Among five hub genes (AXL, SGCE, COL12A1, ANTXR1, LOXL2), COL12A1 and LOXL2 were upregulated in GC tissues. IDO1 disclosed positive correlation with six collagen genes by coefficient matrix diagram. Knockdown of IDO1 decreased the expression of LOXL2, COL6A1, COL6A2 and COL12A1 in GC cells in both mRNA and protein levels. Of them, knockdown of COL12A1 inhibited cell migration more apparently than knockdown of others. IDO1 and COL12A1 revealed synergistic efficacy on promoting cell migration via a positive feedback sustained by MAPK pathway. This bioprocess was mediated by IDO1 metabolite kynurenine and integrin β1. A popliteal lymph nodemetastasis model was established for verifying metastatic promotion of IDO1 and COL12A1 in GC.

conclusionsIDO1 and COL12A1 synergistically promoted GC metastasis. The novel findings suggested that both IDO1 and COL12A1 may be promising targets on anti-cancer treatment in GC.

Indexed as

AnimalsCell Line, TumorCell MovementCollagen Type XIIGene Expression Regulation, NeoplasticHumansIndoleamine-Pyrrole 2,3,-DioxygenaseKynurenineLymphatic MetastasisMAP Kinase Signaling SystemMiceNeoplasm TransplantationStomach NeoplasmsTumor MicroenvironmentUp-RegulationCOL12A1 protein, humanCollagen Type XIIIDO1 protein, humanIndoleamine-Pyrrole 2,3,-DioxygenaseKynurenineCOL12A1Gastric cancerIDO1Lymph node metastasisWGCNA

Identifiers

PMID31315643
PMCPMC6637527
OpenAlexW2961331837

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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.