Evidence map›Paper›PMID 41806318›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

In Vivo CRISPR Screening Identifies the Glutamate Receptor GRIA2 as Promoting Peritoneal Metastasis of Gastric Cancer via Calcium-Dependent β-Catenin Activation.

Jie Sun, Xu Yang, Wenchao Jiang, Chengbo Ji, Yingying Wu, Haoyu Sun, Xinyou Liu, Masami Yamamoto, Tetsuya Tsukamoto, Sachiyo Nomura and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–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

1 citing paper in PubMed.

  1. Article
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

14 authors.

Jie SunDepartment of Gastrointestinal Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Xu YangDepartment of Gastrointestinal Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Wenchao JiangDepartment of Gastrointestinal Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Chengbo JiDepartment of Gastrointestinal Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Yingying WuDepartment of Gastrointestinal Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Haoyu SunDepartment of Gastrointestinal Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Xinyou LiuDepartment of General Surgery, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, Fujian, China.
Masami YamamotoDepartment of Pathology, Nippon Veterinary and Life Science University, Tokyo, Japan.
Tetsuya TsukamotoDepartment of Pathology, Graduate School of Medicine, Fujita Health University, Toyoake, Japan.
Sachiyo NomuraDepartment of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Junjie ZhaoDepartment of Gastrointestinal Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Yuanyuan RuanDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Haojie LiDepartment of Gastrointestinal Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Xuefei WangDepartment of Gastrointestinal Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.

Funding

Scientific Research Foundation of Zhongshan Hospital ZY2024-003
6 · The paper itself

Abstract

Peritoneal metastasis is the most lethal manifestation of gastric cancer, with a median survival of less than one year, highlighting the need for new therapeutic targets. Through an in vivo genome-wide CRISPR/Cas9 screen, we identified GRIA2, an AMPA-type glutamate receptor subunit, as a key driver of peritoneal metastasis. GRIA2 promotes gastric cancer cell migration, invasion, stemness, and adhesion to mesothelial cells in a glutamate-dependent manner. Mechanistically, glutamate activates GRIA2, enhancing its interaction with GSK-3β and inducing calcium influx, inhibiting GSK-3β kinase activity and stabilizing β-catenin, thereby activating the Wnt/β-catenin signaling pathway. Single-cell RNA sequencing revealed that cancer-associated fibroblasts are the primary source of glutamate in the peritoneal microenvironment, which establishes a paracrine axis that enhances GRIA2-driven metastasis. Pharmacological inhibition of AMPA receptors with NBQX and Selurampanel suppressed peritoneal metastasis in both cell line-derived and patient-derived organoid xenograft (PDOX) mouse models. In clinical analysis, GRIA2 expression in peritoneal metastases correlated with the levels of β-catenin and phosphorylated GSK-3β (serine 9), with high GRIA2 expression predicting poor prognosis. These findings suggest that GRIA2 is a novel therapeutic target, and AMPA receptor antagonists are promising agents for treating gastric cancer peritoneal metastasis.

Indexed as

beta CateninCalciumPeritoneal NeoplasmsReceptors, AMPAStomach NeoplasmsAnimalsCell Line, TumorCell MovementCRISPR-Cas SystemsGlycogen Synthase Kinase 3 betaHumansMiceWnt Signaling Pathwaybeta CateninCalciumGlycogen Synthase Kinase 3 betaReceptors, AMPACRISPR screeninggastric cancerGRIA2GSK‐3βperitoneal metastasis

Identifiers

PMID41806318
PMCPMC13185854

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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.