Evidence map›Paper›PMID 40667649›Full record

ArticleJournal of cell science2025

Front-biased activation of the Ras-Rab5-Rac1 loop coordinates collective cell migration.

Yuya Jikko, Eriko Deguchi, Kimiya Matsuda, Naoya Hino, Shinya Tsukiji, Michiyuki Matsuda, Kenta Terai

Abstract read
In one paragraph

Article in Journal of cell science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Decoding Rho GTPase signalling networks in directed cell migration.Frontiers in cell and developmental biology · 2026
    Review
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

7 authors.

Yuya JikkoDepartment of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-Cho, Sakyo-ku, Kyoto 606-8501, Japan.
Eriko DeguchiDepartment of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-Cho, Sakyo-ku, Kyoto 606-8501, Japan.
Kimiya MatsudaCenter for Living Systems Information Sciences, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe-Cho, Sakyo-ku, Kyoto 606-8501, Japan.
Naoya HinoInstitute of Science and Technology Austria, 3400 Klosterneuburg, Austria.
Shinya TsukijiDepartment of Nanopharmaceutical Sciences, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya, Aichi 466-0061, Japan.ORCID 0000-0002-1402-5773
Michiyuki MatsudaDepartment of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-Cho, Sakyo-ku, Kyoto 606-8501, Japan.ORCID 0000-0002-5876-9969
Kenta TeraiDepartment of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-Cho, Sakyo-ku, Kyoto 606-8501, Japan.ORCID 0000-0001-7638-3720

Funding

Core Research for Evolutional Science and Technology JPMJCR1654Japan Science and Technology AgencyJapan Society for the Promotion of Science 19H00993Japan Society for the Promotion of Science 20H05898Japan Society for the Promotion of Science 21H05226Moonshot Research and Development Program JPMJPS2022Tokushima University
6 · The paper itself

Abstract

Collective cell migration is coordinated by the front-to-rear intercellular propagation of EGFR-Ras-ERK pathway activation. However, the molecular mechanisms integrating front-to-rear information into this intercellular signaling cascade, particularly the determinants of cellular front-side specification, remain elusive. We visualized the activity of EGFR, Ras, Rac1 and Rab5A (hereafter Rab5) by using FRET biosensors and chemogenetic tools. Whereas EGFR activation was uniformly observed within cells, Ras activation was biased to the front side within cells. The polarized Ras activation depended on Merlin and Rac1, which also showed front-biased activation. Furthermore, Rab5, a crucial regulator of cell migration, demonstrated similar front-biased activation and was found to function downstream of Ras while being necessary for Rac1 activation. Thus, the positive feedback loop consisting of Ras, Rab5 and Rac1 is activated primarily at the front of collectively migrating cells. These findings offer new spatio-temporal insight into processing front-rear information during collective cell migration.

Indexed as

Cell Movementrab5 GTP-Binding Proteinsrac1 GTP-Binding Proteinras ProteinsAnimalsErbB ReceptorsHumansSignal TransductionErbB Receptorsrab5 GTP-Binding Proteinsrac1 GTP-Binding ProteinRAC1 protein, humanras ProteinsCell migrationCell polarityCollective cell migrationEGFREpidermal growth factor receptorERM family proteinRabRac1Ras protein

Identifiers

PMID40667649
PMCPMC12377714

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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.