Pub Date : 2026-02-02DOI: 10.1016/j.ceb.2026.102613
Owen Ou Ning Hsiu , Randy Yat Choi Poon
The cell cycle is marked by dynamic fluctuations in reactive oxygen species (ROS). While low levels of ROS can stimulate cell proliferation, excessive ROS lead to cell cycle arrest. Notably, cell cycle arrest can further generate more ROS, creating a bidirectional relationship that underscores the necessity for cells to finely tune ROS levels to maintain homeostasis and ensure proper cell cycle progression. Unlike classical cell cycle checkpoint systems, ROS directly oxidise cysteine residues in critical cell cycle regulators, with examples ranging from cyclins and cyclin-dependent kinases to APC/C, CDK inhibitors, and other CDK regulators, altering their functions. This review explores the interplay between ROS and the cell cycle, emphasizing how understanding their relationship could enhance therapeutic outcomes.
{"title":"ROS and the cell cycle: Cycling in and out of the comfort zone of redox control","authors":"Owen Ou Ning Hsiu , Randy Yat Choi Poon","doi":"10.1016/j.ceb.2026.102613","DOIUrl":"10.1016/j.ceb.2026.102613","url":null,"abstract":"<div><div>The cell cycle is marked by dynamic fluctuations in reactive oxygen species (ROS). While low levels of ROS can stimulate cell proliferation, excessive ROS lead to cell cycle arrest. Notably, cell cycle arrest can further generate more ROS, creating a bidirectional relationship that underscores the necessity for cells to finely tune ROS levels to maintain homeostasis and ensure proper cell cycle progression. Unlike classical cell cycle checkpoint systems, ROS directly oxidise cysteine residues in critical cell cycle regulators, with examples ranging from cyclins and cyclin-dependent kinases to APC/C, CDK inhibitors, and other CDK regulators, altering their functions. This review explores the interplay between ROS and the cell cycle, emphasizing how understanding their relationship could enhance therapeutic outcomes.</div></div>","PeriodicalId":50608,"journal":{"name":"Current Opinion in Cell Biology","volume":"99 ","pages":"Article 102613"},"PeriodicalIF":4.3,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098580","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 : 2026-02-01DOI: 10.1016/S0955-0674(26)00009-8
{"title":"Outside Back Cover","authors":"","doi":"10.1016/S0955-0674(26)00009-8","DOIUrl":"10.1016/S0955-0674(26)00009-8","url":null,"abstract":"","PeriodicalId":50608,"journal":{"name":"Current Opinion in Cell Biology","volume":"98 ","pages":"Article 102621"},"PeriodicalIF":4.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077733","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 : 2026-01-22DOI: 10.1016/j.ceb.2025.102612
Tao Wen , Dong Liang , Tao Wang , Wenteng Hu , Yonghong Li , Lei Shi
Long noncoding RNAs (lncRNAs) have traditionally been classified as non-protein-coding transcripts, yet recent advances in ribosome profiling and proteogenomics have revealed that some lncRNAs encode functional micropeptides. These micropeptides, typically fewer than 100 amino acids, play pivotal roles in cancer progression by modulating signaling pathways, metabolic reprogramming, and therapeutic implication. Despite challenges in detection due to their low abundance, emerging technologies like mass spectrometry and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based validation are accelerating their discovery. This review synthesizes current knowledge on lncRNA-derived micropeptides in cancer, emphasizing their mechanisms, clinical implications, and therapeutic promise. By bridging the gap between noncoding RNA biology and proteomics, these micropeptides represent a transformative frontier in cancer research and treatment.
长链非编码rna (lncRNAs)传统上被归类为非蛋白质编码转录物,但最近在核糖体分析和蛋白质基因组学方面的进展表明,一些lncRNAs编码功能性微肽。这些微肽通常少于100个氨基酸,通过调节信号通路、代谢重编程和治疗意义在癌症进展中发挥关键作用。尽管由于它们的丰度较低,在检测方面存在挑战,但质谱和基于CRISPR的短回文重复序列(Clustered Regularly Interspaced Short Palindromic Repeats)验证等新兴技术正在加速它们的发现。本文综述了lncrna衍生的微肽在癌症中的作用,强调了它们的机制、临床意义和治疗前景。通过弥合非编码RNA生物学和蛋白质组学之间的差距,这些微肽代表了癌症研究和治疗的变革前沿。
{"title":"LncRNA-encoded micropeptides: Emerging regulators of cancer metabolism and precision oncology","authors":"Tao Wen , Dong Liang , Tao Wang , Wenteng Hu , Yonghong Li , Lei Shi","doi":"10.1016/j.ceb.2025.102612","DOIUrl":"10.1016/j.ceb.2025.102612","url":null,"abstract":"<div><div>Long noncoding RNAs (lncRNAs) have traditionally been classified as non-protein-coding transcripts, yet recent advances in ribosome profiling and proteogenomics have revealed that some lncRNAs encode functional micropeptides. These micropeptides, typically fewer than 100 amino acids, play pivotal roles in cancer progression by modulating signaling pathways, metabolic reprogramming, and therapeutic implication. Despite challenges in detection due to their low abundance, emerging technologies like mass spectrometry and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based validation are accelerating their discovery. This review synthesizes current knowledge on lncRNA-derived micropeptides in cancer, emphasizing their mechanisms, clinical implications, and therapeutic promise. By bridging the gap between noncoding RNA biology and proteomics, these micropeptides represent a transformative frontier in cancer research and treatment.</div></div>","PeriodicalId":50608,"journal":{"name":"Current Opinion in Cell Biology","volume":"98 ","pages":"Article 102612"},"PeriodicalIF":4.3,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038066","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 : 2026-01-07DOI: 10.1016/j.ceb.2025.102611
Xiao Qin
The progression from healthy tissue to malignancy involves a critical precancerous stage marked by cellular lesions with aberrant molecular and phenotypic characteristics. The fate of these lesions is shaped not only by cell-intrinsic alterations but also by the precancerous microenvironment (PME), an ecosystem of epithelial, stromal and immune cells embedded within the extracellular matrix. Focusing on epithelial precancers, this review first defines the metastable state and signalling networks that distinguish precancer from homeostasis and cancer. It then examines the models and technologies used to investigate PME signalling across spatial–temporal dimensions, followed by an integrated overview of how PME components collectively shape lesion trajectories. Finally, it outlines the outstanding questions and research priorities needed to advance mechanistic insight and realise the translational potential of PME-targeted interventions.
{"title":"Precancerous microenvironment: A signalling perspective","authors":"Xiao Qin","doi":"10.1016/j.ceb.2025.102611","DOIUrl":"10.1016/j.ceb.2025.102611","url":null,"abstract":"<div><div>The progression from healthy tissue to malignancy involves a critical precancerous stage marked by cellular lesions with aberrant molecular and phenotypic characteristics. The fate of these lesions is shaped not only by cell-intrinsic alterations but also by the precancerous microenvironment (PME), an ecosystem of epithelial, stromal and immune cells embedded within the extracellular matrix. Focusing on epithelial precancers, this review first defines the metastable state and signalling networks that distinguish precancer from homeostasis and cancer. It then examines the models and technologies used to investigate PME signalling across spatial–temporal dimensions, followed by an integrated overview of how PME components collectively shape lesion trajectories. Finally, it outlines the outstanding questions and research priorities needed to advance mechanistic insight and realise the translational potential of PME-targeted interventions.</div></div>","PeriodicalId":50608,"journal":{"name":"Current Opinion in Cell Biology","volume":"98 ","pages":"Article 102611"},"PeriodicalIF":4.3,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145925548","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 : 2025-12-24DOI: 10.1016/j.ceb.2025.102602
Shashank Shekhar , Velia M. Fowler , Carol C. Gregorio
Cellular and biochemical studies of actin assembly have long focused primarily on reactions at the fast-growing barbed end of actin filaments. In contrast, the slow-growing pointed end has traditionally received comparatively less attention. Recent structural, biochemical, and cell biological studies have sparked a renaissance in pointed-end research, revealing its active roles in both actin assembly and disassembly. The discovery of pointed-end polymerization by the bacterial effector VopF has challenged the barbed-end centric assembly paradigm and reinvigorated efforts to identify endogenous pointed-end elongators. This review highlights the emerging molecular machinery and mechanisms governing pointed-end dynamics, including nucleation, elongation, capping, and disassembly. We discuss the physiological significance of pointed-end regulation and argue that a comprehensive understanding of actin regulation requires close attention to pointed end dynamics.
{"title":"Renaissance at the actin filament pointed end: Mechanisms of assembly, capping and depolymerization","authors":"Shashank Shekhar , Velia M. Fowler , Carol C. Gregorio","doi":"10.1016/j.ceb.2025.102602","DOIUrl":"10.1016/j.ceb.2025.102602","url":null,"abstract":"<div><div>Cellular and biochemical studies of actin assembly have long focused primarily on reactions at the fast-growing barbed end of actin filaments. In contrast, the slow-growing pointed end has traditionally received comparatively less attention. Recent structural, biochemical, and cell biological studies have sparked a renaissance in pointed-end research, revealing its active roles in both actin assembly and disassembly. The discovery of pointed-end polymerization by the bacterial effector VopF has challenged the barbed-end centric assembly paradigm and reinvigorated efforts to identify endogenous pointed-end elongators. This review highlights the emerging molecular machinery and mechanisms governing pointed-end dynamics, including nucleation, elongation, capping, and disassembly. We discuss the physiological significance of pointed-end regulation and argue that a comprehensive understanding of actin regulation requires close attention to pointed end dynamics.</div></div>","PeriodicalId":50608,"journal":{"name":"Current Opinion in Cell Biology","volume":"98 ","pages":"Article 102602"},"PeriodicalIF":4.3,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145835286","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 : 2025-12-10DOI: 10.1016/j.ceb.2025.102603
Ai Shinobu , Ayaka Nagasato-Ichikawa , Mariko Okada
Signal transduction is a complex system governing cellular behavior across physiological and pathological contexts. Advances in systems biology have positioned cell modeling as a powerful tool for reconstructing the dynamics and trajectories of disease processes. Nevertheless, despite progress in AI-assisted model generation, parameter estimation remains a challenge, especially under data constraints. In contrast, molecular dynamics simulations offer crucial, high-resolution insights by uncovering conformational activation mechanisms and by extracting kinetic parameters; however, they face scalability limitations. This review focuses on modeling of the ErbB signaling system, highlighting recent advances at both the cellular and molecular scales. Emerging trends, such as simulation data reuse, machine learning-guided network inference, and modeling within realistic environmental contexts, are now driving a compelling integration of these molecular and cellular modeling paradigms.
{"title":"Network structures and parameters in multiscale modeling in ErbB signaling networks","authors":"Ai Shinobu , Ayaka Nagasato-Ichikawa , Mariko Okada","doi":"10.1016/j.ceb.2025.102603","DOIUrl":"10.1016/j.ceb.2025.102603","url":null,"abstract":"<div><div>Signal transduction is a complex system governing cellular behavior across physiological and pathological contexts. Advances in systems biology have positioned cell modeling as a powerful tool for reconstructing the dynamics and trajectories of disease processes. Nevertheless, despite progress in AI-assisted model generation, parameter estimation remains a challenge, especially under data constraints. In contrast, molecular dynamics simulations offer crucial, high-resolution insights by uncovering conformational activation mechanisms and by extracting kinetic parameters; however, they face scalability limitations. This review focuses on modeling of the ErbB signaling system, highlighting recent advances at both the cellular and molecular scales. Emerging trends, such as simulation data reuse, machine learning-guided network inference, and modeling within realistic environmental contexts, are now driving a compelling integration of these molecular and cellular modeling paradigms.</div></div>","PeriodicalId":50608,"journal":{"name":"Current Opinion in Cell Biology","volume":"98 ","pages":"Article 102603"},"PeriodicalIF":4.3,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145737566","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 : 2025-12-01DOI: 10.1016/j.ceb.2025.102601
Christina Paraskeva , Athanasia Stavropoulou , Vasiliki Koliaraki
The tumor microenvironment (TME) plays a crucial role in cancer initiation, progression, and metastasis, with cancer-associated fibroblasts (CAFs) representing one of the most abundant and influential stromal cell populations. Recent advances in single cell sequencing and spatial transcriptomics in combination with mechanistic studies have revealed the extent of CAF functional heterogeneity, identifying distinct subpopulations with specialized roles in tumor promotion, immune modulation, and therapy resistance. This review synthesizes current understanding of CAF biology, highlighting recent discoveries regarding their spatial organization, temporal dynamics, and immunoregulatory functions. We discuss emerging therapeutic strategies targeting CAF subpopulations, including approaches for CAF elimination and reprogramming. These advances provide new opportunities for developing more effective cancer treatments that account for stromal complexity and CAF-mediated resistance mechanisms.
{"title":"Cancer-associated fibroblasts: Recent advances and therapeutic implications","authors":"Christina Paraskeva , Athanasia Stavropoulou , Vasiliki Koliaraki","doi":"10.1016/j.ceb.2025.102601","DOIUrl":"10.1016/j.ceb.2025.102601","url":null,"abstract":"<div><div>The tumor microenvironment (TME) plays a crucial role in cancer initiation, progression, and metastasis, with cancer-associated fibroblasts (CAFs) representing one of the most abundant and influential stromal cell populations. Recent advances in single cell sequencing and spatial transcriptomics in combination with mechanistic studies have revealed the extent of CAF functional heterogeneity, identifying distinct subpopulations with specialized roles in tumor promotion, immune modulation, and therapy resistance. This review synthesizes current understanding of CAF biology, highlighting recent discoveries regarding their spatial organization, temporal dynamics, and immunoregulatory functions. We discuss emerging therapeutic strategies targeting CAF subpopulations, including approaches for CAF elimination and reprogramming. These advances provide new opportunities for developing more effective cancer treatments that account for stromal complexity and CAF-mediated resistance mechanisms.</div></div>","PeriodicalId":50608,"journal":{"name":"Current Opinion in Cell Biology","volume":"98 ","pages":"Article 102601"},"PeriodicalIF":4.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645754","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 : 2025-12-01DOI: 10.1016/S0955-0674(25)00148-6
{"title":"Outside Back Cover","authors":"","doi":"10.1016/S0955-0674(25)00148-6","DOIUrl":"10.1016/S0955-0674(25)00148-6","url":null,"abstract":"","PeriodicalId":50608,"journal":{"name":"Current Opinion in Cell Biology","volume":"97 ","pages":"Article 102610"},"PeriodicalIF":4.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145732924","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 : 2025-11-22DOI: 10.1016/j.ceb.2025.102600
Joe J. Tyler, Helen K. Matthews
Ras proteins modulate key cellular signalling pathways and drive excessive proliferation when mutated in cancer. However, they also influence actin cytoskeleton organisation. In the model organism Dictyostelium, domains of active Ras pattern the plasma membrane and locally reorganise the actin cortex, driving the formation of actin-based protrusions. Recent work has identified analogous Ras-dependent actin structures in cancer cells, including actin waves, protrusions and membrane blebs, which promote cell survival and motility. In addition, Ras activation induces changes to signalling networks and gene expression that result in cell-wide changes to actin network architecture, cortex mechanics and cell shape. This review examines how the local and global effects of Ras signalling on the actin cytoskeleton are coordinated and how they contribute to cytoskeletal plasticity during cancer progression.
{"title":"Ras signalling at the actin cortex: Coordinating local and global changes to cell morphology","authors":"Joe J. Tyler, Helen K. Matthews","doi":"10.1016/j.ceb.2025.102600","DOIUrl":"10.1016/j.ceb.2025.102600","url":null,"abstract":"<div><div>Ras proteins modulate key cellular signalling pathways and drive excessive proliferation when mutated in cancer. However, they also influence actin cytoskeleton organisation. In the model organism <em>Dictyostelium,</em> domains of active Ras pattern the plasma membrane and locally reorganise the actin cortex, driving the formation of actin-based protrusions. Recent work has identified analogous Ras-dependent actin structures in cancer cells, including actin waves, protrusions and membrane blebs, which promote cell survival and motility. In addition, Ras activation induces changes to signalling networks and gene expression that result in cell-wide changes to actin network architecture, cortex mechanics and cell shape. This review examines how the local and global effects of Ras signalling on the actin cytoskeleton are coordinated and how they contribute to cytoskeletal plasticity during cancer progression.</div></div>","PeriodicalId":50608,"journal":{"name":"Current Opinion in Cell Biology","volume":"97 ","pages":"Article 102600"},"PeriodicalIF":4.3,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145578606","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 : 2025-11-17DOI: 10.1016/j.ceb.2025.102598
David H. Kim , Shreya E. Boby , Gregory M.I. Redpath, Vaishnavi Ananthanarayanan
Receptor tyrosine kinases and other cell surface receptors are tightly regulated by endocytosis, which controls both the duration and spatial organisation of their downstream signalling. In cancers, altered internalisation and trafficking lead to sustained or misrouted signalling that promotes uncontrolled cell growth and survival. Motor proteins and their cargo adaptors are central to receptor signalling since they determine intracellular endosome positioning, recycling, and degradation. While their roles in intracellular transport have long been studied, the dysfunction of motors and adaptors in the context of aberrant receptor signalling and cancer progression has only recently begun to emerge. In this review, we highlight recent advances in understanding motor and adaptor function in healthy cells, discuss evidence implicating these proteins in oncogenic signalling, and consider how these insights may guide future directions in the field.
{"title":"Driving cancer: Motor and adaptor protein dysregulation in endocytic receptor signalling","authors":"David H. Kim , Shreya E. Boby , Gregory M.I. Redpath, Vaishnavi Ananthanarayanan","doi":"10.1016/j.ceb.2025.102598","DOIUrl":"10.1016/j.ceb.2025.102598","url":null,"abstract":"<div><div>Receptor tyrosine kinases and other cell surface receptors are tightly regulated by endocytosis, which controls both the duration and spatial organisation of their downstream signalling. In cancers, altered internalisation and trafficking lead to sustained or misrouted signalling that promotes uncontrolled cell growth and survival. Motor proteins and their cargo adaptors are central to receptor signalling since they determine intracellular endosome positioning, recycling, and degradation. While their roles in intracellular transport have long been studied, the dysfunction of motors and adaptors in the context of aberrant receptor signalling and cancer progression has only recently begun to emerge. In this review, we highlight recent advances in understanding motor and adaptor function in healthy cells, discuss evidence implicating these proteins in oncogenic signalling, and consider how these insights may guide future directions in the field.</div></div>","PeriodicalId":50608,"journal":{"name":"Current Opinion in Cell Biology","volume":"97 ","pages":"Article 102598"},"PeriodicalIF":4.3,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145551690","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}