Evidence map›Paper›PMID 41690948›Full record

ArticleNature communications2026

Ligand-dependent Wnt signaling promotes gastric cancer metastasis through hyaluronan expression in microenvironment.

Yuichiro Furutani, Hiroko Oshima, Chang Pyo Hong, SeonJu Choi, Ryosuke Machi, Mizuho Nakayama, Kazuhiro Murakami, Shintaro Yagi, Yukinobu Ito, Daichi Maeda and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

13 authors.

Yuichiro Furutani *Division of Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.ORCID http://orcid.org/0000-0002-8258-9773
Hiroko Oshima *Division of Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.ORCID http://orcid.org/0000-0001-6855-4008
Chang Pyo HongYiPSCELL Inc., Seoul, Republic of Korea.ORCID http://orcid.org/0000-0001-5030-1248
SeonJu ChoiYiPSCELL Inc., Seoul, Republic of Korea.ORCID http://orcid.org/0000-0003-1331-3463
Ryosuke MachiDivision of Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.ORCID http://orcid.org/0000-0003-1943-8443
Mizuho NakayamaDivision of Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
Kazuhiro MurakamiDivision of Epithelial Stem Cell Biology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
Shintaro YagiDepartment of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kanazawa University, Kanazawa, Japan.ORCID http://orcid.org/0000-0001-7465-5761
Yukinobu ItoDepartment of Molecular and Cellular Pathology, Kanazawa University, Kanazawa, Japan.
Daichi MaedaDepartment of Molecular and Cellular Pathology, Kanazawa University, Kanazawa, Japan.
Noriyuki InakiDepartment of Gastrointestinal Surgery, Kanazawa University, Kanazawa, Japan.ORCID http://orcid.org/0000-0002-4241-5015
Nick BarkerInstitute of Molecular and Cell Biology (IMCB), A*STAR, Singapore, Singapore.
Masanobu OshimaDivision of Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Japan. oshimam@staff.kanazawa-u.ac.jp.ORCID http://orcid.org/0000-0002-3304-0004

Funding

Japan Agency for Medical Research and Development (AMED) 24ama22152h0002MEXT | Japan Society for the Promotion of Science (JSPS) 22H00454MEXT | Japan Society for the Promotion of Science (JSPS) 23K02899
6 · The paper itself

Abstract

The majority of gastric cancer cells proliferate in a Wnt ligand-dependent manner. To investigate this, we generated mice harboring Kras, Tgfbr2, and Trp53 (KTP) as well as with the same mutations plus Wnt1 expression (WKTP) in gastric mucosa. While KTP mice develop gastric metaplasia, WKTP mice develop dysplastic tumors, highlighting the role of ligand-dependent Wnt signaling in primary tumorigenesis. Organoids derived from WKTP mice form liver metastases following splenic transplantation, whereas KTP organoids do not. Notably, Apc disruption fails to induce metastasis of KTP cells, suggesting that stromal Wnt signaling promotes metastasis. Mechanistically, tumor-derived Wnt ligands cooperate with TGFβ signaling to induce Has2 expression in cancer-associated fibroblasts (CAFs), leading to hyaluronan accumulation in the metastatic microenvironment. Strikingly, hyaluronidase expression in WKTP cells significantly suppresses liver metastasis. Here we show the critical role of ligand-dependent Wnt signaling and Has2-mediated hyaluronan deposition in metastasis, offering potential therapeutic strategy against gastric cancer metastasis.

Indexed as

Hyaluronic AcidStomach NeoplasmsTumor MicroenvironmentWnt Signaling PathwayAnimalsCancer-Associated FibroblastsCell Line, TumorGastric MucosaGene Expression Regulation, NeoplasticHumansHyaluronan SynthasesHyaluronoglucosaminidaseLigandsLiver NeoplasmsMiceReceptor, Transforming Growth Factor-beta Type IIHas2 protein, mouseHyaluronan SynthasesHyaluronic AcidHyaluronoglucosaminidaseLigandsReceptor, Transforming Growth Factor-beta Type IITrp53 protein, mouseTumor Suppressor Protein p53Wnt1 ProteinWnt1 protein, mouse

Identifiers

PMID41690948
PMCPMC13018301

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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.