Evidence map›Paper›PMID 42370534›Full record

ArticleGenes to cells : devoted to molecular & cellular mechanisms2026

FOXO1 Is Required for Growth and Viability of Cancer-Associated Fibroblasts in Human Breast Carcinomas.

Takumi Koyama, Tetsuo Kobayashi, Yoshihiro Mezawa, Weibo Gao, Kaishi Yamada, Kazunari Yamashita, Zixu Wang, Yu Koyama, Masaaki Abe, Reo Maruyama and 12 more

Abstract read
In one paragraph

Article in Genes to cells : devoted to molecular & cellular mechanisms, 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

22 authors.

Takumi KoyamaDepartment of Oral Pathobiological Science and Surgery, Tokyo Dental College, Tokyo, Japan.
Tetsuo KobayashiDepartment of Pathology and Oncology, Juntendo University Faculty of Medicine, Tokyo, Japan.ORCID https://orcid.org/0000-0003-0698-7224
Yoshihiro MezawaDepartment of Pathology and Oncology, Juntendo University Faculty of Medicine, Tokyo, Japan.
Weibo GaoDepartment of Molecular Pathogenesis, Juntendo University Graduate School of Medicine, Tokyo, Japan.ORCID https://orcid.org/0009-0004-3089-5340
Kaishi YamadaDepartment of Pathology and Oncology, Juntendo University Faculty of Medicine, Tokyo, Japan.
Kazunari YamashitaDepartment of Pathology and Oncology, Juntendo University Faculty of Medicine, Tokyo, Japan.
Zixu WangDepartment of Molecular Pathogenesis, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Yu KoyamaDepartment of Oral Pathobiological Science and Surgery, Tokyo Dental College, Tokyo, Japan.
Masaaki AbeDepartment of Pathology and Oncology, Juntendo University Faculty of Medicine, Tokyo, Japan.
Reo MaruyamaDivision of Cancer Epigenomics, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
Liying YangDivision of Cancer Epigenomics, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
Hiroaki DaitokuLife Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki, Japan.
Akiyoshi FukamizuLife Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki, Japan.
Atsushi TakanoResearch Platform Office, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Yohei MiyagiMolecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan.ORCID https://orcid.org/0000-0002-0056-7010
Tomoyuki YokoseDepartment of Pathology, Kanagawa Cancer Center, Yokohama, Japan.
Toshinari YamashitaDepartment of Breast Surgery and Oncology, Kanagawa Cancer Center, Yokohama, Japan.
Keisuke SugaharaDepartment of Oral Pathobiological Science and Surgery, Tokyo Dental College, Tokyo, Japan.
Hiroyuki SeimiyaDivision of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
Yataro DaigoResearch Platform Office, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Akira KatakuraDepartment of Oral Pathobiological Science and Surgery, Tokyo Dental College, Tokyo, Japan.
Akira OrimoDepartment of Pathology and Oncology, Juntendo University Faculty of Medicine, Tokyo, Japan.

Funding

Japan Society for the Promotion of Science 15K14385Japan Society for the Promotion of Science 16H06277Japan Society for the Promotion of Science 18K07207Japan Society for the Promotion of Science 22H04923Japan Society for the Promotion of Science 25640069
6 · The paper itself

Abstract

Carcinoma-associated fibroblasts (CAFs), frequently present in the stroma of human breast carcinomas, influence tumor characteristics. A forkhead box protein O1 (FOXO1) transcription factor is a critical mediator of the cellular responses to oxidative stress in various cell types. However, the roles of FOXO1 in CAFs have been poorly understood. Here, we show more intense FOXO1 staining in stromal fibroblasts in human breast cancers compared to those in non-cancerous regions. Notably, stronger stromal FOXO1 staining is significantly associated with poorer outcomes in 237 breast cancer patients. FOXO1 expression is also more abundant in cultured human breast CAFs compared to the control counterpart human mammary fibroblasts. FOXO1 expression is upregulated in control fibroblasts by malnutrition and hypoxia, suggesting such starvation to mediate increased FOXO1 expression in CAFs. Of note, treatment with AS1842856, a FOXO1 inhibitor, significantly attenuates growth and viability in CAFs relative to control fibroblasts. Suppression of FOXO1 expression by shRNA also substantially inhibits CAFs' growth in culture. When the FOXO1-knockdowned CAFs were implanted with breast cancer cells into recipient mice, the number of these fibroblasts present in developed tumors tends to decrease. Taken together, these findings indicate that FOXO1 expression in human breast CAFs is required for their growth and viability.

Indexed as

Breast NeoplasmsCancer-Associated FibroblastsForkhead Box Protein O1AnimalsCell Line, TumorCell ProliferationCell SurvivalFemaleFibroblastsGene Expression Regulation, NeoplasticHumansMiceForkhead Box Protein O1FOXO1 protein, human

Identifiers

PMID42370534
PMCPMC13356234

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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.