Pub Date : 2026-01-14DOI: 10.1016/j.ejcb.2026.151531
Guangli Wang, Hua Wang, Yuling Wang, Xi Li, Heng Luo, Dongxing Li
{"title":"Corrigendum to \"Polyploid giant cancer cells: A novel target in future cancer therapy\" [Eur. J. Cell Biol. 105/1 (2026) 151529].","authors":"Guangli Wang, Hua Wang, Yuling Wang, Xi Li, Heng Luo, Dongxing Li","doi":"10.1016/j.ejcb.2026.151531","DOIUrl":"https://doi.org/10.1016/j.ejcb.2026.151531","url":null,"abstract":"","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":" ","pages":"151531"},"PeriodicalIF":4.3,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-08DOI: 10.1016/j.ejcb.2026.151530
Dongyan Li, Ruotian Du, Jilong Li, Yi Xie, Yan Huang, Xianghui Gong, Jing Ji
Increased extracellular matrix (ECM) stiffness is a well-recognized pathological hallmark of the trabecular meshwork (TM) in glaucomatous eyes; however, the mechanotransductive pathways by which TM cells sense and respond to mechanical cues remain incompletely understood. In this study, we identified integrin β1 as a key stiffness-responsive molecule, with its fluorescence signal and membrane localization significantly enhanced in human trabecular meshwork cells (hTMCs) cultured on stiffer substrates. Functional blockade of integrin β1 led to a marked reduction in cell proliferation, migration, and phagocytic activity across all stiffness conditions. Notably, the magnitude of blocking effects varied with substrate stiffness: inhibition of proliferative and migratory capacities was more pronounced on rigid substrates, whereas blockade-induced reduction in phagocytic activity was more evident on compliant substrates. These findings suggest that integrin β1 plays a central role in mediating hTMCs responses to biomechanical signals and may contribute to the functional impairment of the TM outflow pathway in the pathogenesis of glaucoma.
{"title":"Integrin β1 mediates mechanosensitive regulation of human trabecular meshwork cell functions in response to substrate stiffness","authors":"Dongyan Li, Ruotian Du, Jilong Li, Yi Xie, Yan Huang, Xianghui Gong, Jing Ji","doi":"10.1016/j.ejcb.2026.151530","DOIUrl":"10.1016/j.ejcb.2026.151530","url":null,"abstract":"<div><div>Increased extracellular matrix (ECM) stiffness is a well-recognized pathological hallmark of the trabecular meshwork (TM) in glaucomatous eyes; however, the mechanotransductive pathways by which TM cells sense and respond to mechanical cues remain incompletely understood. In this study, we identified integrin β1 as a key stiffness-responsive molecule, with its fluorescence signal and membrane localization significantly enhanced in human trabecular meshwork cells (hTMCs) cultured on stiffer substrates. Functional blockade of integrin β1 led to a marked reduction in cell proliferation, migration, and phagocytic activity across all stiffness conditions. Notably, the magnitude of blocking effects varied with substrate stiffness: inhibition of proliferative and migratory capacities was more pronounced on rigid substrates, whereas blockade-induced reduction in phagocytic activity was more evident on compliant substrates. These findings suggest that integrin β1 plays a central role in mediating hTMCs responses to biomechanical signals and may contribute to the functional impairment of the TM outflow pathway in the pathogenesis of glaucoma.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"105 2","pages":"Article 151530"},"PeriodicalIF":4.3,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-27DOI: 10.1016/j.ejcb.2025.151529
Guangli Wang , Hua Wang , Yuling Wang , Xi Li , Heng Luo
Under intense therapeutic stress—including chemotherapy, radiotherapy, and targeted therapies—tumor cells can undergo ploidy reprogramming to generate polyploid giant cancer cells (PGCCs). Once largely overlooked, this rare but biologically distinctive tumor cell subpopulation has now been firmly implicated across multiple malignancies in therapy resistance, metastatic progression, and tumor relapse. PGCCs are characterized by striking morphological and genetic features, including extreme cellular enlargement, multinucleation or high-ploidy states, and profound genomic instability. Importantly, under stress conditions, PGCCs can undergo depolyploidization to produce progeny with enhanced adaptive fitness. This review systematically synthesizes the major mechanisms underlying PGCC formation, including endoreplication, mitotic slippage, cytokinesis failure, cell fusion, and entosis, highlighting their contextual cooperation and temporal continuity across diverse stress environments and genetic backgrounds. We further delineate the core functional roles of PGCCs in tumor biology, with a particular focus on their contributions to therapeutic tolerance, metastasis promotion, and cancer stem cell–like properties, and critically examine their intimate links to intratumoral heterogeneity and tumor evolutionary dynamics. Building on these insights, we evaluate emerging therapeutic strategies targeting PGCCs and discuss current methodological challenges and future directions in their detection, multi-omics characterization, and machine learning–assisted identification.Collectively, PGCCs represent a pivotal stress-adapted cellular state that drives ongoing tumor evolution under therapeutic pressure. A deeper mechanistic understanding of PGCC biology may provide a conceptual framework and novel intervention strategies to overcome cancer resistance and recurrence.
在强烈的治疗压力下，包括化疗、放疗和靶向治疗，肿瘤细胞可以进行倍体重编程，产生多倍体巨癌细胞（polyploid giant cancer cells, pgcc）。这种罕见但生物学上独特的肿瘤细胞亚群曾经被广泛忽视，但现在已与多种恶性肿瘤的治疗耐药、转移进展和肿瘤复发密切相关。pgcc具有显著的形态和遗传特征，包括极端的细胞扩大，多核或高倍性状态，以及深刻的基因组不稳定性。重要的是，在胁迫条件下，pgcc可以进行去多倍体化，产生具有增强适应适应度的后代。本文系统地综合了PGCC形成的主要机制，包括内复制、有丝分裂滑移、细胞质分裂失败、细胞融合和内吞，强调了它们在不同应激环境和遗传背景下的上下文合作和时间连续性。我们进一步描述了pgcc在肿瘤生物学中的核心功能作用，特别关注它们对治疗耐受性、促进转移和癌症干细胞样特性的贡献，并严格检查它们与肿瘤内异质性和肿瘤进化动力学的密切联系。基于这些见解，我们评估了针对pgcc的新兴治疗策略，并讨论了当前的方法挑战和未来的方向，包括检测、多组学表征和机器学习辅助鉴定。总的来说，pgcc代表了一种关键的应激适应细胞状态，在治疗压力下驱动持续的肿瘤进化。对PGCC生物学的更深入的机制理解可能提供一个概念性框架和新的干预策略，以克服癌症的耐药和复发。
{"title":"Polyploid giant cancer cells: A novel target in future cancer therapy","authors":"Guangli Wang , Hua Wang , Yuling Wang , Xi Li , Heng Luo","doi":"10.1016/j.ejcb.2025.151529","DOIUrl":"10.1016/j.ejcb.2025.151529","url":null,"abstract":"<div><div>Under intense therapeutic stress—including chemotherapy, radiotherapy, and targeted therapies—tumor cells can undergo ploidy reprogramming to generate polyploid giant cancer cells (PGCCs). Once largely overlooked, this rare but biologically distinctive tumor cell subpopulation has now been firmly implicated across multiple malignancies in therapy resistance, metastatic progression, and tumor relapse. PGCCs are characterized by striking morphological and genetic features, including extreme cellular enlargement, multinucleation or high-ploidy states, and profound genomic instability. Importantly, under stress conditions, PGCCs can undergo depolyploidization to produce progeny with enhanced adaptive fitness. This review systematically synthesizes the major mechanisms underlying PGCC formation, including endoreplication, mitotic slippage, cytokinesis failure, cell fusion, and entosis, highlighting their contextual cooperation and temporal continuity across diverse stress environments and genetic backgrounds. We further delineate the core functional roles of PGCCs in tumor biology, with a particular focus on their contributions to therapeutic tolerance, metastasis promotion, and cancer stem cell–like properties, and critically examine their intimate links to intratumoral heterogeneity and tumor evolutionary dynamics. Building on these insights, we evaluate emerging therapeutic strategies targeting PGCCs and discuss current methodological challenges and future directions in their detection, multi-omics characterization, and machine learning–assisted identification.Collectively, PGCCs represent a pivotal stress-adapted cellular state that drives ongoing tumor evolution under therapeutic pressure. A deeper mechanistic understanding of PGCC biology may provide a conceptual framework and novel intervention strategies to overcome cancer resistance and recurrence.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"105 1","pages":"Article 151529"},"PeriodicalIF":4.3,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-24DOI: 10.1016/j.ejcb.2025.151528
Sofia R. Parisi, Danielle Z. Harte, Jeremy C. Simpson
The human skeletal disease Smith McCort dysplasia is known to be caused by mutations in the RAB33B gene. Despite there being detailed genetic and medical studies about the patients carrying these mutated genes, there is a paucity of information about these mutations at the molecular and cellular level. The RAB33B gene encodes the small GTP binding protein Rab33b, which primarily localises to the Golgi apparatus in cells, and plays roles in membrane traffic and autophagy. In recent years, several different mutations in the RAB33B gene have been reported, potentially giving rise to both prematurely truncated proteins and also proteins containing single amino acid substitutions. Importantly, no work to date has examined the consequences of expression of these Rab33b variants in cells. In the study presented here we use a model cell culture system to seek to understand what the consequences might be to cells expressing five of the reported disease-causing Rab33b variants. We specifically examine the ectopic expression of two truncated and three single amino acid substitution variants in cultured cells. Our results reveal that all of these mutants show subcellular mislocalisation and fail to accumulate on Golgi membranes. We also demonstrate that each of these mutants are unstable and suffer from premature degradation in cells. Finally, overexpression of the single amino acid substitution variants in cells induced for autophagy causes a severe reduction in the number of autophagosomes as defined by the number of LC3B-positive puncta. Our results provide the first molecular insight into the cellular effects caused by five of the reported Rab33b mutants that give rise to Smith McCort dysplasia.
{"title":"Mutations in the Rab33b protein that lead to the skeletal disease Smith-McCort dysplasia result in unstable proteins and altered autophagy function","authors":"Sofia R. Parisi, Danielle Z. Harte, Jeremy C. Simpson","doi":"10.1016/j.ejcb.2025.151528","DOIUrl":"10.1016/j.ejcb.2025.151528","url":null,"abstract":"<div><div>The human skeletal disease Smith McCort dysplasia is known to be caused by mutations in the <em>RAB33B</em> gene. Despite there being detailed genetic and medical studies about the patients carrying these mutated genes, there is a paucity of information about these mutations at the molecular and cellular level. The <em>RAB33B</em> gene encodes the small GTP binding protein Rab33b, which primarily localises to the Golgi apparatus in cells, and plays roles in membrane traffic and autophagy. In recent years, several different mutations in the <em>RAB33B</em> gene have been reported, potentially giving rise to both prematurely truncated proteins and also proteins containing single amino acid substitutions. Importantly, no work to date has examined the consequences of expression of these Rab33b variants in cells. In the study presented here we use a model cell culture system to seek to understand what the consequences might be to cells expressing five of the reported disease-causing Rab33b variants. We specifically examine the ectopic expression of two truncated and three single amino acid substitution variants in cultured cells. Our results reveal that all of these mutants show subcellular mislocalisation and fail to accumulate on Golgi membranes. We also demonstrate that each of these mutants are unstable and suffer from premature degradation in cells. Finally, overexpression of the single amino acid substitution variants in cells induced for autophagy causes a severe reduction in the number of autophagosomes as defined by the number of LC3B-positive puncta. Our results provide the first molecular insight into the cellular effects caused by five of the reported Rab33b mutants that give rise to Smith McCort dysplasia.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"105 1","pages":"Article 151528"},"PeriodicalIF":4.3,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145921451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-18DOI: 10.1016/j.ejcb.2025.151527
Diego Liviu Boaru , Diego De Leon-Oliva , Oscar Fraile-Martinez , Patricia De Castro-Martinez , Cielo Garcia-Montero , Connie Ferrara-Coppola , Majd N. Michael Alhaddadin , Silvestra Barrena-Blázquez , Cristina De las Peñas-González , Noemí Holgado-Tirado , Mónica Tordesillas-Vicente , Diego Torres-Carranza , Laura Lopez-Gonzalez , Raul Diaz-Pedrero , Melchor Alvarez-Mon , Miguel A. Saez , Miguel A. Ortega
Lysyl oxidase (LOXs) are copper-dependent enzymes traditionally known for catalyzing the cross-linking of collagen and elastin, thereby ensuring extracellular matrix (ECM) stability. However, growing evidence reveals that their biological functions extend far beyond ECM remodeling. This review highlights the diverse roles of the LOX family, comprising LOX, LOXL1, LOXL2, LOXL3, and LOXL4, in tissue repair, vascular remodeling, inflammation, and cancer. Each isoform exhibits unique structural domains, regulatory pathways, and functional interactions with signaling cascades such as TGF-β, PDGF, VEGF, and HIF-1α. LOXs are essential for wound healing, coordinating ECM synthesis and cross-linking during different phases of tissue regeneration. Their expression is tightly modulated by inflammatory cytokines, and their dysregulation has been implicated in pathological fibrosis and impaired tissue repair. In cancer, LOXs contribute to epithelial-to-mesenchymal transition (EMT), cell invasion, and metastasis through both enzymatic and non-enzymatic mechanisms, including intracellular signaling, Snail1 stabilization, and cytoskeletal modulation. They also influence angiogenesis by regulating VEGF expression and promoting endothelial cell activation via PDGFRβ-AKT signaling. Intracellular and nuclear functions further expand their impact on gene regulation and chromatin structure. Given their involvement in matrix dynamics, mechanotransduction, and cell fate determination, LOXs emerge as key players in both physiological and pathological contexts. Understanding their multifactorial roles opens potential avenues for therapeutic targeting in cancer, fibrosis, and chronic inflammatory diseases.
{"title":"The role of the LOX family in cancer","authors":"Diego Liviu Boaru , Diego De Leon-Oliva , Oscar Fraile-Martinez , Patricia De Castro-Martinez , Cielo Garcia-Montero , Connie Ferrara-Coppola , Majd N. Michael Alhaddadin , Silvestra Barrena-Blázquez , Cristina De las Peñas-González , Noemí Holgado-Tirado , Mónica Tordesillas-Vicente , Diego Torres-Carranza , Laura Lopez-Gonzalez , Raul Diaz-Pedrero , Melchor Alvarez-Mon , Miguel A. Saez , Miguel A. Ortega","doi":"10.1016/j.ejcb.2025.151527","DOIUrl":"10.1016/j.ejcb.2025.151527","url":null,"abstract":"<div><div>Lysyl oxidase (LOXs) are copper-dependent enzymes traditionally known for catalyzing the cross-linking of collagen and elastin, thereby ensuring extracellular matrix (ECM) stability. However, growing evidence reveals that their biological functions extend far beyond ECM remodeling. This review highlights the diverse roles of the LOX family, comprising LOX, LOXL1, LOXL2, LOXL3, and LOXL4, in tissue repair, vascular remodeling, inflammation, and cancer. Each isoform exhibits unique structural domains, regulatory pathways, and functional interactions with signaling cascades such as TGF-β, PDGF, VEGF, and HIF-1α. LOXs are essential for wound healing, coordinating ECM synthesis and cross-linking during different phases of tissue regeneration. Their expression is tightly modulated by inflammatory cytokines, and their dysregulation has been implicated in pathological fibrosis and impaired tissue repair. In cancer, LOXs contribute to epithelial-to-mesenchymal transition (EMT), cell invasion, and metastasis through both enzymatic and non-enzymatic mechanisms, including intracellular signaling, Snail1 stabilization, and cytoskeletal modulation. They also influence angiogenesis by regulating VEGF expression and promoting endothelial cell activation via PDGFRβ-AKT signaling. Intracellular and nuclear functions further expand their impact on gene regulation and chromatin structure. Given their involvement in matrix dynamics, mechanotransduction, and cell fate determination, LOXs emerge as key players in both physiological and pathological contexts. Understanding their multifactorial roles opens potential avenues for therapeutic targeting in cancer, fibrosis, and chronic inflammatory diseases.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"105 1","pages":"Article 151527"},"PeriodicalIF":4.3,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-16DOI: 10.1016/j.ejcb.2025.151526
Pei-Chen Lu , Ruth Rollason , Chia-An Chou , Valeryia Kuzmuk , Kate J. Heesom , Moin A. Saleem , Gavin I. Welsh
Nephrotic syndrome is frequently associated with pathogenic variants in NPHS2 (podocin), including the common and severe R138Q substitution. Using conditionally immortalized human podocytes expressing Myc-tagged podocin variants (G92C, V180M, R138Q, R238S, and R291W), we systematically compared variant-specific defects in plasma-membrane trafficking, detergent-resistant microdomain (DRM) localization, and protein stability. All variants displayed reduced plasma membrane abundance and altered DRM distribution. Among them, R138Q-podocin showed uniquely reduced protein stability. Consistent with previous reports, quantitative proteomics revealed a strong enrichment of endoplasmic reticulum (ER) quality-control and ubiquitin–proteasome components in the R138Q interactome, confirming its identity as an ER-associated degradation substrate. Proteasome inhibition with MG132 stabilized R138Q-podocin and restored its trafficking to both the plasma membrane and DRMs, indicating that impaired stability—rather than an intrinsic trafficking defect—restricts its surface localization. Proteomic profiling further identified caveolin-1, CDCP1, and myosin VI as previously unrecognized podocin interactors. These findings expand the podocin interaction network and suggest potential roles in adhesion-associated membrane organization. Collectively, these results demonstrate that pathogenic podocin variants disrupt podocyte function through distinct mechanisms involving degradation, trafficking, and membrane microdomain association, providing insight into variant-specific disease pathways in nephrotic syndrome.
Synopsis
This study examined the trafficking, membrane localization, and stability of disease-associated podocin variants. All variants showed reduced plasma-membrane abundance and altered detergent-resistant microdomain distribution, whereas only R138Q-podocin exhibited marked proteasomal degradation. Quantitative proteomics confirmed the endoplasmic reticulum-associated degradation signature of R138Q and identified caveolin-1, CDCP1, and myosin VI as previously unrecognized podocin interactors. These findings reveal variant-specific mechanisms governing podocin stability and membrane organization.
{"title":"Pathogenic podocin variants exhibit distinct defects in trafficking, membrane organization, and degradation pathways","authors":"Pei-Chen Lu , Ruth Rollason , Chia-An Chou , Valeryia Kuzmuk , Kate J. Heesom , Moin A. Saleem , Gavin I. Welsh","doi":"10.1016/j.ejcb.2025.151526","DOIUrl":"10.1016/j.ejcb.2025.151526","url":null,"abstract":"<div><div>Nephrotic syndrome is frequently associated with pathogenic variants in <em>NPHS2</em> (podocin), including the common and severe R138Q substitution. Using conditionally immortalized human podocytes expressing Myc-tagged podocin variants (G92C, V180M, R138Q, R238S, and R291W), we systematically compared variant-specific defects in plasma-membrane trafficking, detergent-resistant microdomain (DRM) localization, and protein stability. All variants displayed reduced plasma membrane abundance and altered DRM distribution. Among them, R138Q-podocin showed uniquely reduced protein stability. Consistent with previous reports, quantitative proteomics revealed a strong enrichment of endoplasmic reticulum (ER) quality-control and ubiquitin–proteasome components in the R138Q interactome, confirming its identity as an ER-associated degradation substrate. Proteasome inhibition with MG132 stabilized R138Q-podocin and restored its trafficking to both the plasma membrane and DRMs, indicating that impaired stability—rather than an intrinsic trafficking defect—restricts its surface localization. Proteomic profiling further identified caveolin-1, CDCP1, and myosin VI as previously unrecognized podocin interactors. These findings expand the podocin interaction network and suggest potential roles in adhesion-associated membrane organization. Collectively, these results demonstrate that pathogenic podocin variants disrupt podocyte function through distinct mechanisms involving degradation, trafficking, and membrane microdomain association, providing insight into variant-specific disease pathways in nephrotic syndrome.</div></div><div><h3>Synopsis</h3><div>This study examined the trafficking, membrane localization, and stability of disease-associated podocin variants. All variants showed reduced plasma-membrane abundance and altered detergent-resistant microdomain distribution, whereas only R138Q-podocin exhibited marked proteasomal degradation. Quantitative proteomics confirmed the endoplasmic reticulum-associated degradation signature of R138Q and identified caveolin-1, CDCP1, and myosin VI as previously unrecognized podocin interactors. These findings reveal variant-specific mechanisms governing podocin stability and membrane organization.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"105 1","pages":"Article 151526"},"PeriodicalIF":4.3,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-02DOI: 10.1016/j.ejcb.2025.151524
Gréta Bányai , Márton Bese Naszlady , János Juhász , András Horváth , Balázs Hegedűs , Tamás Garay
Video microscopy-based single-cell migration analysis allows for precise measurement of cell migration by extracting a range of migration parameters from tracking data during analysis. This study aimed to enhance our understanding of the behavior and sensitivity of these parameters themselves. Random walk simulations and analysis of experimental data were utilized to analyze the sensitivity of migration parameters to tracking methods (manual and semi-automatic), and to assess the repeatability of these parameters. Additionally, the influence of cell line-specific characteristics on migration outcomes was examined.
Our results demonstrate that displacement-based parameters – mean squared displacement (MSD), displacement (D), and maximal displacement (Max D) – are robust in detecting migration effects but are profoundly influenced by cell line-specific properties, particularly with semi-automatic tracking. These metrics are especially valuable when analyzing data from different, non-identical tracking methods. In contrast, path-based parameters – such as total traveled distance (TTD), velocity (V), and average velocity (AV) – are more sensitive to subtle treatment effects, but are prone to noise from tracking methods and inherently insensitive to treatment-induced changes in directionality.
Our findings emphasize the importance of combining path-based and displacement-based metrics in video microscopy analyses to achieve a comprehensive picture of cell migration dynamics.
{"title":"Revisiting single-cell migration parameters from 2D video microscopic measurements","authors":"Gréta Bányai , Márton Bese Naszlady , János Juhász , András Horváth , Balázs Hegedűs , Tamás Garay","doi":"10.1016/j.ejcb.2025.151524","DOIUrl":"10.1016/j.ejcb.2025.151524","url":null,"abstract":"<div><div>Video microscopy-based single-cell migration analysis allows for precise measurement of cell migration by extracting a range of migration parameters from tracking data during analysis. This study aimed to enhance our understanding of the behavior and sensitivity of these parameters themselves. Random walk simulations and analysis of experimental data were utilized to analyze the sensitivity of migration parameters to tracking methods (manual and semi-automatic), and to assess the repeatability of these parameters. Additionally, the influence of cell line-specific characteristics on migration outcomes was examined.</div><div>Our results demonstrate that displacement-based parameters – mean squared displacement (MSD), displacement (D), and maximal displacement (Max D) – are robust in detecting migration effects but are profoundly influenced by cell line-specific properties, particularly with semi-automatic tracking. These metrics are especially valuable when analyzing data from different, non-identical tracking methods. In contrast, path-based parameters – such as total traveled distance (TTD), velocity (V), and average velocity (AV) – are more sensitive to subtle treatment effects, but are prone to noise from tracking methods and inherently insensitive to treatment-induced changes in directionality.</div><div>Our findings emphasize the importance of combining path-based and displacement-based metrics in video microscopy analyses to achieve a comprehensive picture of cell migration dynamics.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"105 1","pages":"Article 151524"},"PeriodicalIF":4.3,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145665356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.ejcb.2025.151523
Sepideh Parvanian , John E. Eriksson
Vimentin, a type III intermediate filament protein, has gained recognition as a multifunctional regulator within the tumor microenvironment (TME). While traditionally considered a hallmark of epithelial-to-mesenchymal transition (EMT), vimentin is increasingly understood as a structural and signaling hub essential for the functional complexity of mesoderm-derived and EMT-transitioned cells. It bridges cytoskeletal architecture with key signaling networks, linking cellular plasticity to mechanotransduction, immune modulation, and metabolic regulation. This unique versatility underlies vimentin’s essential role in supporting the migratory, remodeling, and adaptive behaviors required in contexts such as wound healing, inflammation, and tissue remodeling—capabilities that cancer cells have co-opted to their advantage. Indeed, vimentin’s pervasive expression across aggressive cancers reflects its ability to scaffold and coordinate the cytoskeletal and signaling rewiring needed for malignancy. This review provides an integrated overview of vimentin’s diverse roles in the TME, emphasizing its contributions to tumor invasiveness, immune regulation, and metabolic adaptation. We conclude by discussing how these insights may inform the development of vimentin-centered strategies to improve therapeutic outcomes in cancer.
{"title":"Vimentin in the tumor microenvironment: orchestrating invasion, immunity, and metabolism","authors":"Sepideh Parvanian , John E. Eriksson","doi":"10.1016/j.ejcb.2025.151523","DOIUrl":"10.1016/j.ejcb.2025.151523","url":null,"abstract":"<div><div>Vimentin, a type III intermediate filament protein, has gained recognition as a multifunctional regulator within the tumor microenvironment (TME). While traditionally considered a hallmark of epithelial-to-mesenchymal transition (EMT), vimentin is increasingly understood as a structural and signaling hub essential for the functional complexity of mesoderm-derived and EMT-transitioned cells. It bridges cytoskeletal architecture with key signaling networks, linking cellular plasticity to mechanotransduction, immune modulation, and metabolic regulation. This unique versatility underlies vimentin’s essential role in supporting the migratory, remodeling, and adaptive behaviors required in contexts such as wound healing, inflammation, and tissue remodeling—capabilities that cancer cells have co-opted to their advantage. Indeed, vimentin’s pervasive expression across aggressive cancers reflects its ability to scaffold and coordinate the cytoskeletal and signaling rewiring needed for malignancy. This review provides an integrated overview of vimentin’s diverse roles in the TME, emphasizing its contributions to tumor invasiveness, immune regulation, and metabolic adaptation. We conclude by discussing how these insights may inform the development of vimentin-centered strategies to improve therapeutic outcomes in cancer.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 4","pages":"Article 151523"},"PeriodicalIF":4.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145620329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.ejcb.2025.151510
Maria Salvador-Mira , Paula Gimenez-Moya , Alba Manso-Aznar , Ester Sánchez-Córdoba , Manuel A. Sevilla-Diez , Veronica Chico , Ivan Nombela , Sara Puente-Marin , Nerea Roher , Luis Perez , Tanja Dučić , Núria Benseny-Cases , Ana Joaquina Perez-Berna , Maria del Mar Ortega-Villaizan
{"title":"Corrigendum to “Viral vaccines promote endoplasmic reticulum stress-induced unfolding protein response in teleost erythrocytes” [Eur. J. Cell Biol. 104 (2025) 151490]","authors":"Maria Salvador-Mira , Paula Gimenez-Moya , Alba Manso-Aznar , Ester Sánchez-Córdoba , Manuel A. Sevilla-Diez , Veronica Chico , Ivan Nombela , Sara Puente-Marin , Nerea Roher , Luis Perez , Tanja Dučić , Núria Benseny-Cases , Ana Joaquina Perez-Berna , Maria del Mar Ortega-Villaizan","doi":"10.1016/j.ejcb.2025.151510","DOIUrl":"10.1016/j.ejcb.2025.151510","url":null,"abstract":"","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 4","pages":"Article 151510"},"PeriodicalIF":4.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144845023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-03DOI: 10.1016/j.ejcb.2025.151522
Marta Rocha , Jonas Petsch , Dorothea Schultheis , Michaela M. Zrelski , Petra Fichtinger , Inga Koneczny , Samuel Meier-Menches , Gerhard Wiche , Rolf Schröder , Lilli Winter
Plectin, a highly versatile and multifunctional cytolinker, acts as a central connector of the intermediate filament (IF) and other cytoskeletal systems. In skeletal muscle, plectin orchestrates and anchors the extrasarcomeric desmin filament network to sites of strategic importance and thereby substantially contributes to its fundamental biomechanical properties. Lack of plectin in skeletal muscle leads to a faulty organization of the desmin IFs, thereby inflicting a reduced mechanical stress tolerance and a progressive myopathic process. Accordingly, the morphological hallmark of the skeletal muscle pathology in most plectinopathies, including epidermolysis bullosa simplex with muscular dystrophy (EBS-MD), is the accumulation of desmin-positive protein aggregates. To address the consequences of plectin-deficiency on other types of IFs, RNA and protein expression as well as localization of various IF subtypes was evaluated in muscle tissue from wild-type and muscle-specific conditional plectin knockout (MCK-Cre/cKO) mice. Notably, vimentin and syncoilin, as well as several other IF subtypes, were significantly upregulated in MCK-Cre/cKO muscles and accumulated in subsarcolemmal and sarcoplasmic areas. In plectin-deficient mouse myoblasts, increased expression levels of vimentin were accompanied by the formation of thickened IF bundles. Primary human myoblasts, treated with the plectin inhibitor plecstatin-1, displayed increased bundling of desmin and vimentin, thus supporting the notion of drastic structural and organizational changes in the network. Finally, we were able to demonstrate the presence of vimentin-positive protein aggregates in skeletal muscle specimens from EBS-MD patients. Together, these data indicate that the depletion of plectin in muscle unequivocally affected the expression and localization of various types of IFs.
{"title":"Consequences of plectin ablation on the various intermediate filament systems in skeletal muscle","authors":"Marta Rocha , Jonas Petsch , Dorothea Schultheis , Michaela M. Zrelski , Petra Fichtinger , Inga Koneczny , Samuel Meier-Menches , Gerhard Wiche , Rolf Schröder , Lilli Winter","doi":"10.1016/j.ejcb.2025.151522","DOIUrl":"10.1016/j.ejcb.2025.151522","url":null,"abstract":"<div><div>Plectin, a highly versatile and multifunctional cytolinker, acts as a central connector of the intermediate filament (IF) and other cytoskeletal systems. In skeletal muscle, plectin orchestrates and anchors the extrasarcomeric desmin filament network to sites of strategic importance and thereby substantially contributes to its fundamental biomechanical properties. Lack of plectin in skeletal muscle leads to a faulty organization of the desmin IFs, thereby inflicting a reduced mechanical stress tolerance and a progressive myopathic process. Accordingly, the morphological hallmark of the skeletal muscle pathology in most plectinopathies, including epidermolysis bullosa simplex with muscular dystrophy (EBS-MD), is the accumulation of desmin-positive protein aggregates. To address the consequences of plectin-deficiency on other types of IFs, RNA and protein expression as well as localization of various IF subtypes was evaluated in muscle tissue from wild-type and muscle-specific conditional plectin knockout (MCK-Cre/cKO) mice. Notably, vimentin and syncoilin, as well as several other IF subtypes, were significantly upregulated in MCK-Cre/cKO muscles and accumulated in subsarcolemmal and sarcoplasmic areas. In plectin-deficient mouse myoblasts, increased expression levels of vimentin were accompanied by the formation of thickened IF bundles. Primary human myoblasts, treated with the plectin inhibitor plecstatin-1, displayed increased bundling of desmin and vimentin, thus supporting the notion of drastic structural and organizational changes in the network. Finally, we were able to demonstrate the presence of vimentin-positive protein aggregates in skeletal muscle specimens from EBS-MD patients. Together, these data indicate that the depletion of plectin in muscle unequivocally affected the expression and localization of various types of IFs.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 4","pages":"Article 151522"},"PeriodicalIF":4.3,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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