Evidence map›Paper›PMID 40745121›Full record

ArticleAnnals of surgical oncology2025

Inhibition of ACVR1 in Cancer-Associated Fibroblasts Suppresses Colorectal Cancer Cell Growth.

Shinya Kato, Norikatsu Miyoshi, Shiki Fujino, Masafumi Horie, Shinichi Yachida, Mitsunobu Takeda, Yuki Sekido, Tsuyoshi Hata, Atsushi Hamabe, Takayuki Ogino and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of surgical oncology, 2025. 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

16 authors.

Shinya KatoDepartment of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Norikatsu MiyoshiDepartment of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan. nmiyoshi@gesurg.med.osaka-u.ac.jp.ORCID http://orcid.org/0000-0003-1113-8884
Shiki FujinoDepartment of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Masafumi HorieDepartment of Molecular and Cellular Pathology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
Shinichi YachidaDepartment of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan.
Mitsunobu TakedaDepartment of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Yuki SekidoDepartment of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Tsuyoshi HataDepartment of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Atsushi HamabeDepartment of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Takayuki OginoDepartment of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Mamoru UemuraDepartment of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Hirofumi YamamotoDepartment of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Masayoshi YasuiDepartment of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan.
Masayuki OhueDepartment of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan.
Yuichiro DokiDepartment of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Hidetoshi EguchiDepartment of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.

Funding

Japan Society for the Promotion of Science 22K08824
6 · The paper itself

Abstract

backgroundColorectal cancer (CRC) is the third most common malignancy worldwide and a leading cause of cancer-related mortality. Stromal signatures in CRC are correlated with poor prognosis and resistance to chemotherapy, affecting tumor progression and relapse. Although single-cell analyses have identified subpopulations of cancer-associated fibroblasts (CAFs), effective molecular targeted therapies against CAFs are lacking. MATERIALS AND

methodsWe employed organoid culture methods, focusing on two-dimensional organoids (2DOs) to mimic CRC histology. Using single-cell analysis, we investigated cancer-fibroblast crosstalk, with emphasis on activin receptor type I (ACVR1) in fibroblasts and bone morphogenetic protein 7 (BMP7) in cancer cells as potential therapeutic targets. The correlation between high ACVR1 and BMP7 expression levels and the prognosis of patients with stage II cancer was evaluated.

resultsThe 2DO mouse xenograft model replicated the characteristics of the fibroblast subpopulations present in human CRC tumors. Single-cell RNA sequencing identified fibroblast clusters, with the BMP7-ACVR1 axis emerging as a potential therapeutic target. High BMP7 and ACVR1 expression was significantly correlated with poor disease-free survival and overall survival in stage II CRC. Administration of an ACVR1 inhibitor during the coculture of 2DOs and mouse stromal cells inhibited tumor growth.

conclusionsACVR1 is a promising therapeutic target that inhibits CAF proliferation. High BMP7 and ACVR1 expression is a significant prognostic factor in stage II CRC.

Indexed as

Activin Receptors, Type IBone Morphogenetic Protein 7Cancer-Associated FibroblastsColorectal NeoplasmsAnimalsBiomarkers, TumorCell ProliferationFemaleHumansMaleMiceMice, NudeOrganoidsPrognosisSurvival RateTumor Cells, CulturedActivin Receptors, Type IACVR1 protein, humanBiomarkers, TumorBMP7 protein, humanBone Morphogenetic Protein 7ACRV1BMP7–ACRV1 axisCancer-associated fibroblastColorectal cancerOrganoid cultureTumor growth inhibitionTwo-dimensional organoid

Identifiers

PMID40745121
PMCPMC12454473

What Socratic holds

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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 Socratic graph.