Evidence map›Paper›PMID 34663724›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2021

The membrane-linked adaptor FRS2β fashions a cytokine-rich inflammatory microenvironment that promotes breast cancer carcinogenesis.

Yasuto Takeuchi, Natsuko Kimura, Takahiko Murayama, Yukino Machida, Daisuke Iejima, Tatsunori Nishimura, Minoru Terashima, Yuming Wang, Mengjiao Li, Reiko Sakamoto and 15 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.6field-weighted citation impact, top 39% of its field
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

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. 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

25 authors at 8 institutions in 1 country.

Yasuto TakeuchiDivision of Cancer Cell Biology, Cancer Research Institute, Institute for Frontier Science Initiative, Kanazawa University, Kanazawa 920-1192, Japan.
Natsuko KimuraDivision of Molecular Therapy, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
Takahiko MurayamaDivision of Cancer Cell Biology, Cancer Research Institute, Institute for Frontier Science Initiative, Kanazawa University, Kanazawa 920-1192, Japan.ORCID 0000-0003-0764-8646
Yukino MachidaDivision of Molecular Therapy, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
Daisuke IejimaDivision of Molecular Therapy, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
Tatsunori NishimuraDivision of Cancer Cell Biology, Cancer Research Institute, Institute for Frontier Science Initiative, Kanazawa University, Kanazawa 920-1192, Japan.
Minoru TerashimaDivision of Functional Genomics, Cancer Research Institute, Institute for Frontier Science Initiative, Kanazawa University, Kanazawa 920-1192, Japan.ORCID 0000-0002-5688-5181
Yuming WangDivision of Cancer Cell Biology, Cancer Research Institute, Institute for Frontier Science Initiative, Kanazawa University, Kanazawa 920-1192, Japan.
Mengjiao LiDivision of Cancer Cell Biology, Cancer Research Institute, Institute for Frontier Science Initiative, Kanazawa University, Kanazawa 920-1192, Japan.
Reiko SakamotoLaboratory of Developmental Genetics, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
Mizuki YamamotoDivision of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
Naoki ItanoDepartment of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kyoto 603-8555, Japan.ORCID 0000-0002-9276-7959
Yusuke InoueDepartment of Diagnostic Radiology, Kitasato University of School of Medicine, Sagamihara City 252-0373, Japan.ORCID 0000-0001-7250-8303
Masataka ItoDepartment of Anatomy, National Defense Medical College, Tokorozawa 359-8513, Japan.
Nobuaki YoshidaLaboratory of Developmental Genetics, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
Jun-Ichiro InoueDivision of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
Koichi AkashiDepartment of Medicine and Biosystemic Science, Graduate School of Medicine, Kyushu University, Fukuoka 812-8582, Japan.
Hideyuki SayaDivision of Gene Regulation, Institute of Advanced Medical Research, Keio University, Tokyo 160-8582, Japan.
Koji FujitaDepartment of Molecular Pathology, Tokyo Medical University, Tokyo 160-8402, Japan.
Masahiko KurodaDepartment of Molecular Pathology, Tokyo Medical University, Tokyo 160-8402, Japan.
Issay KitabayashiDivision of Hematological Malignancy, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Dominic VoonCancer Research Institute, Institute for Frontier Science Initiative, Kanazawa University, Kanazawa 920-1192, Japan.
Takeshi SuzukiDivision of Functional Genomics, Cancer Research Institute, Institute for Frontier Science Initiative, Kanazawa University, Kanazawa 920-1192, Japan.ORCID 0000-0002-1737-0900
Arinobu TojoDivision of Molecular Therapy, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.ORCID 0000-0001-9016-1948
Noriko GotohDivision of Cancer Cell Biology, Cancer Research Institute, Institute for Frontier Science Initiative, Kanazawa University, Kanazawa 920-1192, Japan; ngotoh@staff.kanazawa-u.ac.jp.ORCID 0000-0003-3733-260X
Kanazawa University · JPThe University of Tokyo · JPTokyo Medical University · JPKeio University · JPKitasato University · JPKyoto Sangyo University · JPKyushu University · JPNational Defense Medical College · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Although it is held that proinflammatory changes precede the onset of breast cancer, the underlying mechanisms remain obscure. Here, we demonstrate that FRS2β, an adaptor protein expressed in a small subset of epithelial cells, triggers the proinflammatory changes that induce stroma in premalignant mammary tissues and is responsible for the disease onset. FRS2β deficiency in mouse mammary tumor virus (MMTV)-ErbB2 mice markedly attenuated tumorigenesis. Importantly, tumor cells derived from MMTV-ErbB2 mice failed to generate tumors when grafted in the FRS2β-deficient premalignant tissues. We found that colocalization of FRS2β and the NEMO subunit of the IκB kinase complex in early endosomes led to activation of nuclear factor-κB (NF-κB), a master regulator of inflammation. Moreover, inhibition of the activities of the NF-κB-induced cytokines, CXC chemokine ligand 12 and insulin-like growth factor 1, abrogated tumorigenesis. Human breast cancer tissues that express higher levels of FRS2β contain more stroma. The elucidation of the FRS2β-NF-κB axis uncovers a molecular link between the proinflammatory changes and the disease onset.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsBreast NeoplasmsCarcinogenesisCytokinesErb-b2 Receptor Tyrosine KinasesFemaleHumansInflammationMammary Neoplasms, ExperimentalMammary Tumor Virus, MouseMiceMice, KnockoutNF-kappa BPregnancyRetroviridae InfectionsAdaptor Proteins, Signal TransducingCytokinesErbb2 protein, mouseErb-b2 Receptor Tyrosine KinasesFRS3 protein, humanFrs3 protein, mouseNF-kappa Bbreast cancercancer-associated fibroblastsFRS3NF-κBpremalignant inflammation

Identifiers

PMID34663724
PMCPMC8639355
OpenAlexW3207337512

What OpenQuestion 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 OpenQuestion graph.