Evidence map›Paper›PMID 40451897›Full record

ArticleScientific reports2025

Downregulation of cGAS/STING expression in tumor cells by cancer-associated fibroblasts in colorectal cancer.

Ryo Kanoda, Shotaro Nakajima, Hirokazu Okayama, Akinao Kaneta, Shun Chida, Takuro Matsumoto, Katsuharu Saito, Tomohiro Kikuchi, Yuya Maruyama, Hiroya Suzuki and 7 more

Abstract read
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

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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

17 authors.

Ryo KanodaDepartment of Gastrointestinal Tract Surgery, School of Medicine, Fukushima Medical University, Fukushima, Japan.
Shotaro NakajimaDepartment of Gastrointestinal Tract Surgery, School of Medicine, Fukushima Medical University, Fukushima, Japan. ipsho555@gmail.com.ORCID http://orcid.org/0000-0002-9339-3792
Hirokazu OkayamaDepartment of Gastrointestinal Tract Surgery, School of Medicine, Fukushima Medical University, Fukushima, Japan.
Akinao KanetaDepartment of Gastrointestinal Tract Surgery, School of Medicine, Fukushima Medical University, Fukushima, Japan.
Shun ChidaDepartment of Gastrointestinal Tract Surgery, School of Medicine, Fukushima Medical University, Fukushima, Japan.
Takuro MatsumotoDepartment of Gastrointestinal Tract Surgery, School of Medicine, Fukushima Medical University, Fukushima, Japan.ORCID http://orcid.org/0000-0001-5589-8573
Katsuharu SaitoDepartment of Gastrointestinal Tract Surgery, School of Medicine, Fukushima Medical University, Fukushima, Japan.
Tomohiro KikuchiDepartment of Gastrointestinal Tract Surgery, School of Medicine, Fukushima Medical University, Fukushima, Japan.
Yuya MaruyamaDepartment of Gastrointestinal Tract Surgery, School of Medicine, Fukushima Medical University, Fukushima, Japan.
Hiroya SuzukiDepartment of Gastrointestinal Tract Surgery, School of Medicine, Fukushima Medical University, Fukushima, Japan.
Kosaku MimuraDepartment of Gastrointestinal Tract Surgery, School of Medicine, Fukushima Medical University, Fukushima, Japan.
Motonobu SaitoDepartment of Gastrointestinal Tract Surgery, School of Medicine, Fukushima Medical University, Fukushima, Japan.ORCID http://orcid.org/0000-0001-5072-3520
Hiroyuki HanayamaDepartment of Gastrointestinal Tract Surgery, School of Medicine, Fukushima Medical University, Fukushima, Japan.
Wataru SakamotoDepartment of Gastrointestinal Tract Surgery, School of Medicine, Fukushima Medical University, Fukushima, Japan.
Tomoyuki MommaDepartment of Gastrointestinal Tract Surgery, School of Medicine, Fukushima Medical University, Fukushima, Japan.
Zenichiro SazeDepartment of Gastrointestinal Tract Surgery, School of Medicine, Fukushima Medical University, Fukushima, Japan.
Koji KonoDepartment of Gastrointestinal Tract Surgery, School of Medicine, Fukushima Medical University, Fukushima, Japan.

Funding

Japan Society for the Promotion of Science 22K08779Japan Society for the Promotion of Science 23K08177
6 · The paper itself

Abstract

The tumor cell-intrinsic cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is critical for activating anti-tumor immunity and enhancing immune checkpoint blockade therapy in colorectal cancer (CRC). Cancer-associated fibroblasts (CAFs), key components of the CRC tumor microenvironment, negatively regulate the anti-tumor immune response. However, their impact on tumor cell-intrinsic cGAS-STING expression remains unclear. In the present study, we investigated whether CAFs can downregulate cGAS-STING expression in CRC. We found that cGAS-STING expression in tumor cells inversely correlated with stromal expression of versican (VCAN), an immunosuppressive CAF marker, in CRC tissues. Co-culture experiments using primary human CAFs derived from CRC tissues revealed that CAFs downregulated cGAS and/or STING expression in CRC cell lines (WiDr, LoVo, HCT116). Furthermore, CAFs expressing VCAN and fibronectin 1 appeared to mediate this suppression. These findings suggest that immunosuppressive CAFs contribute to the downregulation of tumor cell-intrinsic cGAS-STING expression in CRC. Therefore, targeting CAFs to restore cGAS-STING expression may represent a promising strategy to enhance the efficacy of CRC treatment.

Indexed as

Cancer-Associated FibroblastsColorectal NeoplasmsMembrane ProteinsNucleotidyltransferasesCell Line, TumorCoculture TechniquesCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseDown-RegulationFemaleFibronectinsGene Expression Regulation, NeoplasticHCT116 CellsHumansMaleSTING ProteinTumor MicroenvironmentcGAS protein, humanCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseFibronectinsMembrane ProteinsNucleotidyltransferasesSTING1 protein, humanSTING ProteinVersicansCancer-associated fibroblastColorectal cancerTumor cell-intrinsic cGAS–STINGVersican

Identifiers

PMID40451897
PMCPMC12127464

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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.