{"title":"Espin enhances confined cell migration by promoting filopodia formation and contributes to cancer metastasis.","authors":"Yan Wang, Peng Shi, Geyao Liu, Wei Chen, Ya-Jun Wang, Yiping Hu, Ao Yang, Tonghua Wei, Yu-Chen Chen, Ling Liang, Zheng Liu, Yan-Jun Liu, Congying Wu","doi":"10.1038/s44319-025-00437-1","DOIUrl":null,"url":null,"abstract":"<p><p>Genes regulating the finger-like cellular protrusions-filopodia have long been implicated in cancer metastasis. However, depleting the flat lamellipodia but retaining filopodia drastically hampers cell migration on spread surface, obscuring the role of filopodia in cell motility. It has been noticed recently that cells under confinement may employ distinct migratory machineries. However, the regulating factors have mainly been focused on cell blebbing, nuclear deformation and cell rear contractility, without much emphasis on cell protrusions and even less on filopodia. Here, by micropore-based screening, we identified espin as an active regulator for confined migration and that its overexpression was associated with metastasis. In comparison to fascin, espin showed stronger actin bundling in vitro and induced shorter and thicker filopodia in cells. Combining the imaging-compatible microchannels and DNA-based tension probes, we uncovered that espin overexpression induced excessive filopodia at the leading edge and along the sides, exerting force for confined migration. Our results demonstrate an important role for filopodia and the regulating protein-espin in confined cell migration and shed new light on cytoskeletal mechanisms underlying metastasis.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"2574-2596"},"PeriodicalIF":6.5000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117036/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"EMBO Reports","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s44319-025-00437-1","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/4 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Genes regulating the finger-like cellular protrusions-filopodia have long been implicated in cancer metastasis. However, depleting the flat lamellipodia but retaining filopodia drastically hampers cell migration on spread surface, obscuring the role of filopodia in cell motility. It has been noticed recently that cells under confinement may employ distinct migratory machineries. However, the regulating factors have mainly been focused on cell blebbing, nuclear deformation and cell rear contractility, without much emphasis on cell protrusions and even less on filopodia. Here, by micropore-based screening, we identified espin as an active regulator for confined migration and that its overexpression was associated with metastasis. In comparison to fascin, espin showed stronger actin bundling in vitro and induced shorter and thicker filopodia in cells. Combining the imaging-compatible microchannels and DNA-based tension probes, we uncovered that espin overexpression induced excessive filopodia at the leading edge and along the sides, exerting force for confined migration. Our results demonstrate an important role for filopodia and the regulating protein-espin in confined cell migration and shed new light on cytoskeletal mechanisms underlying metastasis.
期刊介绍：
EMBO Reports is a scientific journal that specializes in publishing research articles in the fields of molecular biology, cell biology, and developmental biology. The journal is known for its commitment to publishing high-quality, impactful research that provides novel physiological and functional insights. These insights are expected to be supported by robust evidence, with independent lines of inquiry validating the findings.
The journal's scope includes both long and short-format papers, catering to different types of research contributions. It values studies that:
Communicate major findings: Articles that report significant discoveries or advancements in the understanding of biological processes at the molecular, cellular, and developmental levels.
Confirm important findings: Research that validates or supports existing knowledge in the field, reinforcing the reliability of previous studies.
Refute prominent claims: Studies that challenge or disprove widely accepted ideas or hypotheses in the biosciences, contributing to the correction and evolution of scientific understanding.
Present null data: Papers that report negative results or findings that do not support a particular hypothesis, which are crucial for the scientific process as they help to refine or redirect research efforts.
EMBO Reports is dedicated to maintaining high standards of scientific rigor and integrity, ensuring that the research it publishes contributes meaningfully to the advancement of knowledge in the life sciences. By covering a broad spectrum of topics and encouraging the publication of both positive and negative results, the journal plays a vital role in promoting a comprehensive and balanced view of scientific inquiry.
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