Pub Date : 2025-03-06DOI: 10.1016/j.ceb.2025.102490
Jinghui Cao , Cai Liang , Hongtao Yu
Aneuploidy is prevalent in cancer and has complicated roles in tumorigenesis. Paradoxically, artificially engineered aneuploidy in normal cells reduces cellular fitness by inducing proteotoxic and genotoxic stresses. A better molecular understanding of the multifaceted roles of aneuploidy in cancer evolution offers promising avenues for future cancer therapies. Here, we discuss the patterns and consequences of aneuploidy in human cancer. We highlight recent efforts to explore aneuploidy as a cancer vulnerability and new interventions that exploit this vulnerability for cancer treatment.
{"title":"Aneuploidy as a cancer vulnerability","authors":"Jinghui Cao , Cai Liang , Hongtao Yu","doi":"10.1016/j.ceb.2025.102490","DOIUrl":"10.1016/j.ceb.2025.102490","url":null,"abstract":"<div><div>Aneuploidy is prevalent in cancer and has complicated roles in tumorigenesis. Paradoxically, artificially engineered aneuploidy in normal cells reduces cellular fitness by inducing proteotoxic and genotoxic stresses. A better molecular understanding of the multifaceted roles of aneuploidy in cancer evolution offers promising avenues for future cancer therapies. Here, we discuss the patterns and consequences of aneuploidy in human cancer. We highlight recent efforts to explore aneuploidy as a cancer vulnerability and new interventions that exploit this vulnerability for cancer treatment.</div></div>","PeriodicalId":50608,"journal":{"name":"Current Opinion in Cell Biology","volume":"94 ","pages":"Article 102490"},"PeriodicalIF":6.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143561959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-03DOI: 10.1016/S0955-0674(25)00038-9
{"title":"Outside Back Cover","authors":"","doi":"10.1016/S0955-0674(25)00038-9","DOIUrl":"10.1016/S0955-0674(25)00038-9","url":null,"abstract":"","PeriodicalId":50608,"journal":{"name":"Current Opinion in Cell Biology","volume":"93 ","pages":"Article 102500"},"PeriodicalIF":6.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-26DOI: 10.1016/j.ceb.2025.102486
Lori B. Koch, Adele L. Marston
Meiosis generates gametes through a specialised cell cycle that reduces the genome by half. Homologous chromosomes are segregated in meiosis I and sister chromatids are segregated in meiosis II. Centromeres and kinetochores play central roles in instructing this specialised chromosome segregation pattern. Accordingly, kinetochores acquire meiosis-specific modifications. Here we contextualise recent highlights in our understanding of how centromeres and kinetochores direct the sorting of chromosomes into gametes via meiosis.
{"title":"The functional organisation of the centromere and kinetochore during meiosis","authors":"Lori B. Koch, Adele L. Marston","doi":"10.1016/j.ceb.2025.102486","DOIUrl":"10.1016/j.ceb.2025.102486","url":null,"abstract":"<div><div>Meiosis generates gametes through a specialised cell cycle that reduces the genome by half. Homologous chromosomes are segregated in meiosis I and sister chromatids are segregated in meiosis II. Centromeres and kinetochores play central roles in instructing this specialised chromosome segregation pattern. Accordingly, kinetochores acquire meiosis-specific modifications. Here we contextualise recent highlights in our understanding of how centromeres and kinetochores direct the sorting of chromosomes into gametes via meiosis.</div></div>","PeriodicalId":50608,"journal":{"name":"Current Opinion in Cell Biology","volume":"94 ","pages":"Article 102486"},"PeriodicalIF":6.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-24DOI: 10.1016/j.ceb.2025.102487
Alice Amitrano , Debanik Choudhury , Konstantinos Konstantopoulos
Cell migration through confined spaces is a critical process influenced by the complex three-dimensional (3D) architecture of the local microenvironment and the surrounding extracellular matrix (ECM). Cells in vivo experience diverse fluidic signals, such as extracellular fluid viscosity, hydraulic resistance, and shear forces, as well as solid cues, like ECM stiffness and viscoelasticity. These fluidic and solid stressors activate mechanotransduction processes and regulate cell migration. They also drive metabolic reprogramming, dynamically altering glycolysis and oxidative phosphorylation to meet the cell's energy demands in different microenvironments. This review discusses recent advances on the mechanisms of cell migration in confinement and how confinement-induced cellular behavior leads to metabolic reprogramming.
{"title":"Navigating confinement: Mechanotransduction and metabolic adaptation","authors":"Alice Amitrano , Debanik Choudhury , Konstantinos Konstantopoulos","doi":"10.1016/j.ceb.2025.102487","DOIUrl":"10.1016/j.ceb.2025.102487","url":null,"abstract":"<div><div>Cell migration through confined spaces is a critical process influenced by the complex three-dimensional (3D) architecture of the local microenvironment and the surrounding extracellular matrix (ECM). Cells <em>in vivo</em> experience diverse fluidic signals, such as extracellular fluid viscosity, hydraulic resistance, and shear forces, as well as solid cues, like ECM stiffness and viscoelasticity. These fluidic and solid stressors activate mechanotransduction processes and regulate cell migration. They also drive metabolic reprogramming, dynamically altering glycolysis and oxidative phosphorylation to meet the cell's energy demands in different microenvironments. This review discusses recent advances on the mechanisms of cell migration in confinement and how confinement-induced cellular behavior leads to metabolic reprogramming.</div></div>","PeriodicalId":50608,"journal":{"name":"Current Opinion in Cell Biology","volume":"94 ","pages":"Article 102487"},"PeriodicalIF":6.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Recent technological advances in proteomics and microscopy techniques, such as cryo-electron microscopy (cryoEM) and expansion microscopy (ExM), have enhanced our understanding of centrosome structure, biogenesis, and regulation. Here we discuss new insights into centrosome structure, highlight new regulatory mechanisms in centrosome biogenesis, and explore emerging concepts in centrosome maintenance and plasticity across different contexts. Furthermore, we review how centrosome biogenesis and homeostasis are dysregulated in various pathological conditions. We finalise by outlining outstanding questions in the field, how the mechanisms discussed are regulated across multiple contexts, the balance between centriole stability and plasticity, and the therapeutic potential of targeting centrosome dysfunction in disease.
{"title":"Centrosome biogenesis and maintenance in homeostasis and disease","authors":"Camila Fernandes-Mariano , Joana N. Bugalhão , Diana Santos , Mónica Bettencourt-Dias","doi":"10.1016/j.ceb.2025.102485","DOIUrl":"10.1016/j.ceb.2025.102485","url":null,"abstract":"<div><div>Recent technological advances in proteomics and microscopy techniques, such as cryo-electron microscopy (cryoEM) and expansion microscopy (ExM), have enhanced our understanding of centrosome structure, biogenesis, and regulation. Here we discuss new insights into centrosome structure, highlight new regulatory mechanisms in centrosome biogenesis, and explore emerging concepts in centrosome maintenance and plasticity across different contexts. Furthermore, we review how centrosome biogenesis and homeostasis are dysregulated in various pathological conditions. We finalise by outlining outstanding questions in the field, how the mechanisms discussed are regulated across multiple contexts, the balance between centriole stability and plasticity, and the therapeutic potential of targeting centrosome dysfunction in disease.</div></div>","PeriodicalId":50608,"journal":{"name":"Current Opinion in Cell Biology","volume":"94 ","pages":"Article 102485"},"PeriodicalIF":6.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-20DOI: 10.1016/j.ceb.2025.102482
Amanda Bentley-DeSousa , Devin Clegg , Shawn M. Ferguson
Limited understanding of regulatory mechanisms controlling LRRK2 kinase activity has hindered insights into both its normal biology and how its dysregulation contributes to Parkinson's disease. Fortunately, recent years have yielded an increased understanding of how LRRK2 kinase activity is dynamically regulated by recruitment to endolysosomal membranes. Notably, multiple small GTPases from the Rab family act as both activators and substrates of LRRK2. Additionally, it was recently discovered that LRRK2 is recruited to, and activated at, stressed or damaged lysosomes through an interaction with GABARAP via the CASM (conjugation of ATG8 to single membranes) pathway. These discoveries position LRRK2 within the rapidly growing field of lysosomal damage and repair mechanisms, offering important insights into lysosome biology and the pathogenesis of Parkinson's disease.
{"title":"LRRK2, lysosome damage, and Parkinson's disease","authors":"Amanda Bentley-DeSousa , Devin Clegg , Shawn M. Ferguson","doi":"10.1016/j.ceb.2025.102482","DOIUrl":"10.1016/j.ceb.2025.102482","url":null,"abstract":"<div><div>Limited understanding of regulatory mechanisms controlling LRRK2 kinase activity has hindered insights into both its normal biology and how its dysregulation contributes to Parkinson's disease. Fortunately, recent years have yielded an increased understanding of how LRRK2 kinase activity is dynamically regulated by recruitment to endolysosomal membranes. Notably, multiple small GTPases from the Rab family act as both activators and substrates of LRRK2. Additionally, it was recently discovered that LRRK2 is recruited to, and activated at, stressed or damaged lysosomes through an interaction with GABARAP via the CASM (conjugation of ATG8 to single membranes) pathway. These discoveries position LRRK2 within the rapidly growing field of lysosomal damage and repair mechanisms, offering important insights into lysosome biology and the pathogenesis of Parkinson's disease.</div></div>","PeriodicalId":50608,"journal":{"name":"Current Opinion in Cell Biology","volume":"93 ","pages":"Article 102482"},"PeriodicalIF":6.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143444348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-20DOI: 10.1016/j.ceb.2025.102484
André Marques , Ines A. Drinnenberg
Centromeres are essential chromosomal regions responsible for ensuring proper chromosome segregation during cell division. Unlike monocentric chromosomes, which have a single centromeric region, holocentric chromosomes distribute centromeric activity along their entire length. This unique organization poses intriguing questions about its structure, function, and evolutionary origins. In this review, we outline recent advances in characterizing the molecular architectures of holocentric chromosomes in mitosis and meiosis, emphasizing both the shared features and lineage-specific adaptations that have evolved in plants and insects. A more detailed characterization of holocentric architectures across different lineages will also offer valuable insights into the potential mechanisms driving the evolutionary transition from monocentric to holocentric chromosomes.
{"title":"Same but different: Centromere regulations in holocentric insects and plants","authors":"André Marques , Ines A. Drinnenberg","doi":"10.1016/j.ceb.2025.102484","DOIUrl":"10.1016/j.ceb.2025.102484","url":null,"abstract":"<div><div>Centromeres are essential chromosomal regions responsible for ensuring proper chromosome segregation during cell division. Unlike monocentric chromosomes, which have a single centromeric region, holocentric chromosomes distribute centromeric activity along their entire length. This unique organization poses intriguing questions about its structure, function, and evolutionary origins. In this review, we outline recent advances in characterizing the molecular architectures of holocentric chromosomes in mitosis and meiosis, emphasizing both the shared features and lineage-specific adaptations that have evolved in plants and insects. A more detailed characterization of holocentric architectures across different lineages will also offer valuable insights into the potential mechanisms driving the evolutionary transition from monocentric to holocentric chromosomes.</div></div>","PeriodicalId":50608,"journal":{"name":"Current Opinion in Cell Biology","volume":"93 ","pages":"Article 102484"},"PeriodicalIF":6.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vimentin, a type III intermediate filament (IF) protein, is well-recognized for its role at the intersection of structural biology and cellular dynamics, influencing various pathways that determine cell fate and function. While these functions have been extensively characterized, there is still limited understanding of vimentin's broader impact beyond its traditional cytoskeletal roles in regulating a spectrum of cellular processes. This review explores the novel and unconventional roles of vimentin, with a focus on its extracellular functions, membrane receptor properties, and regulatory influence on gene expression and cellular metabolism.
{"title":"The unconventional role of vimentin intermediate filaments","authors":"Xinyi Huang , Shuangshuang Zhao , Yifan Xing , Xuedi Gao , Chenglin Miao , Yuhan Huang , Yaming Jiu","doi":"10.1016/j.ceb.2025.102483","DOIUrl":"10.1016/j.ceb.2025.102483","url":null,"abstract":"<div><div>Vimentin, a type III intermediate filament (IF) protein, is well-recognized for its role at the intersection of structural biology and cellular dynamics, influencing various pathways that determine cell fate and function. While these functions have been extensively characterized, there is still limited understanding of vimentin's broader impact beyond its traditional cytoskeletal roles in regulating a spectrum of cellular processes. This review explores the novel and unconventional roles of vimentin, with a focus on its extracellular functions, membrane receptor properties, and regulatory influence on gene expression and cellular metabolism.</div></div>","PeriodicalId":50608,"journal":{"name":"Current Opinion in Cell Biology","volume":"93 ","pages":"Article 102483"},"PeriodicalIF":6.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143444426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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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