Espin enhances confined cell migration by promoting filopodia formation and contributes to cancer metastasis

被引：0

作者：

Wang, Yan ^{[1
,2
]}

Shi, Peng ^{[3
]}

Liu, Geyao ^{[1
,2
]}

Chen, Wei ^{[4
]}

Wang, Ya-Jun ^{[5
]}

Hu, Yiping ^{[1
,2
]}

Yang, Ao ^{[6
]}

Wei, Tonghua ^{[1
,2
]}

Chen, Yu-Chen ^{[5
]}

Liang, Ling ^{[6
]}

Liu, Zheng ^{[4
]}

Liu, Yan-Jun ^{[5
]}

Wu, Congying ^{[1
,2
]}

机构：

[1] Peking Univ Hlth Sci Ctr, Inst Syst Biomed, Sch Basic Med Sci, Beijing 100191, Peoples R China

[2] Peking Univ Hlth Sci Ctr, Int Canc Inst, Beijing Key Lab Tumor Syst Biol, Beijing 100191, Peoples R China

[3] Soochow Univ, Canc Inst, Suzhou Med Coll, Suzhou 215000, Jiangsu, Peoples R China

[4] Wuhan Univ, Inst Adv Studies, Hubei Key Lab Cell Homeostasis, TaiKang Ctr Life & Med Sci,Coll Life Sci, Wuhan 430072, Hubei, Peoples R China

[5] Fudan Univ, Shanghai Xuhui Cent Hosp, Zhongshan Xuhui Hosp, Shanghai Key Lab Med Epigenet,Inst Biomed Sci, Shanghai 200032, Peoples R China

[6] Peking Univ Hlth Sci Ctr, Sch Basic Med Sci, Dept Biophys, Beijing 100191, Peoples R China

来源：

EMBO REPORTS | 2025年 / 26卷 / 10期

基金：

中国国家自然科学基金; 中国博士后科学基金; 国家重点研发计划;

关键词：

Cancer Metastasis; Confined Migration; Espin; Filopodia; MYOSIN-X; MOLECULAR MOTOR; 3D MIGRATION; EXPRESSION; ADHESION; LAMELLIPODIA; BARRIER; ARP2/3;

D O I：

10.1038/s44319-025-00437-1

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：2574 / 2596

页数：23

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