{"title":"Epigenetic drivers of metalloproteinases and metastasis.","authors":"Marco Seehawer, Kornelia Polyak","doi":"10.1016/j.tcb.2025.02.010","DOIUrl":"https://doi.org/10.1016/j.tcb.2025.02.010","url":null,"abstract":"<p><p>Metalloproteinases (MPs) are crucial for development and homeostasis due to their diverse physiological functions, from the cellular to the organismal level. Their activity is tightly regulated at multiple levels, including epigenetic regulation through DNA methylation and histone modifications. Aberrant MP expression can result in pathological events, involving extracellular matrix remodeling, which can facilitate cancer cell invasion and dissemination. As clinical testing of MP inhibitors has been limited by toxicity, alternative approaches are needed. Epigenetically-driven MP expression is often specific to cancer cells, giving an enticing possibility for cancer cell-specific targeting. Moreover, aberrant epigenetic activity can also drive other metastatic events. Therefore, targeting the epigenetic regulators of MP expression may be a promising alternative approach for the prevention and treatment of metastatic disease.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Design principles of gene circuits for longevity.","authors":"Paula Godoy, Nan Hao","doi":"10.1016/j.tcb.2025.02.006","DOIUrl":"https://doi.org/10.1016/j.tcb.2025.02.006","url":null,"abstract":"<p><p>Aging is a dynamic process that is driven by cellular damage and disruption of homeostatic gene regulatory networks (GRNs). Traditional studies often focus on individual genes, but understanding their interplay is key to unraveling the mechanisms of aging. This review explores the gene circuits that influence longevity and highlights the role of feedback loops in maintaining cellular balance. The SIR2-HAP circuit in yeast serves as a model to explore how mutual inhibition between pathways influences aging trajectories and how engineering stable fixed points or oscillations within these circuits can extend lifespan. Feedback loops crucial for maintaining homeostasis are also reviewed, and we highlight how their destabilization accelerates aging. By leveraging systems and synthetic biology, strategies are proposed that may stabilize these loops within single cells, thereby enhancing their resilience to aging-related damage.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cellular homeostatic responses to lysosomal damage.","authors":"Jingyue Jia, Suttinee Poolsup, Jay E Salinas","doi":"10.1016/j.tcb.2025.02.007","DOIUrl":"https://doi.org/10.1016/j.tcb.2025.02.007","url":null,"abstract":"<p><p>Lysosomes are essential membrane-bound organelles that control cellular homeostasis by integrating intracellular functions with external signals. Their critical roles make lysosomal membranes vulnerable to rupture under various stressors, leading to cellular dysfunction. However, the mechanisms by which cells respond to lysosomal damage have only recently begun to be explored. In this review, we summarize the cellular mechanisms activated by lysosomal damage, emphasizing those that restore lysosomal integrity and sustain homeostasis, including recognition, repair, removal, replacement, and remodeling. Drawing on our expertise, we provide an in-depth focus on the remodeling process involved in these responses, including metabolic signaling and stress granule formation. Finally, we discuss the implications of lysosomal damage in human diseases, underscoring potential therapeutic strategies to preserve lysosomal function and alleviate related disorders.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Quality control of mitochondrial nucleoids.","authors":"Hao Liu, Haixia Zhuang, Du Feng","doi":"10.1016/j.tcb.2025.02.005","DOIUrl":"https://doi.org/10.1016/j.tcb.2025.02.005","url":null,"abstract":"<p><p>Mitochondrial nucleoids, organized complexes that house and protect mitochondrial DNA (mtDNA), are normally confined within the mitochondrial double-membrane system. Under cellular stress conditions, particularly oxidative and inflammatory stress, these nucleoids can undergo structural alterations that lead to their aberrant release into the cytoplasm. This mislocalization of nucleoid components, especially mtDNA, can trigger inflammatory responses and cell death pathways, highlighting the critical importance of nucleoid quality control mechanisms. The release of mitochondrial nucleoids occurs through specific membrane channels and transport pathways, fundamentally disrupting cellular homeostasis. Cells have evolved multiple clearance mechanisms to manage cytoplasmic nucleoids, including nuclease-mediated degradation, lysosomal elimination, and cellular excretion. This review examines the molecular mechanisms governing nucleoid quality control and explores the delicate balance between mitochondrial biology and cellular immunity. Our analysis provides insights that could inform therapeutic strategies for mtDNA-associated diseases and inflammatory disorders.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Autophagy-dependent versus autophagy-independent ferroptosis.","authors":"Ye Zhu, Motoki Fujimaki, David C Rubinsztein","doi":"10.1016/j.tcb.2025.01.005","DOIUrl":"https://doi.org/10.1016/j.tcb.2025.01.005","url":null,"abstract":"<p><p>Ferroptosis is an iron-dependent cell death pathway that, until recently, has been considered to be dependent on autophagy. However, recent studies have reported conflicting results, raising the question about which cell contexts determine the roles of autophagy in ferroptosis. This opinion article addresses this question by summarizing the contexts and/or diseases in which autophagy is a driver or suppressor of ferroptosis. The execution of ferroptosis depends on levels of (labile) iron, unsaturated (phospho)lipids and free radicals. We propose that the cell context in which these three factors and/or their upstream pathways are differentially regulated dictates whether autophagy positively or negatively regulates ferroptosis.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The gain and loss of plasticity during development and evolution.","authors":"Amber Q Rock, Mansi Srivastava","doi":"10.1016/j.tcb.2025.01.008","DOIUrl":"https://doi.org/10.1016/j.tcb.2025.01.008","url":null,"abstract":"<p><p>Studies of embryonic plasticity, which were foundational for developmental biology, revealed variation across species and patterns of association with cleavage programs and adult regenerative capacity. Modern molecular and genetic tools now enable a reexamination of these classical experiments in diverse species and have the potential to reveal mechanisms that regulate plasticity over developmental time. This review synthesizes previous work on plasticity in embryos and adults and associated genetic mechanisms, providing a framework to organize data from a wide range of species. Mechanisms that explain how plasticity is lost in mammalian embryos are highlighted and crystallize a proposal for future studies in new research organisms that could identify shared principles for embryonic plasticity and, potentially, its maintenance into adulthood.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Trends in Cell BiologyPub Date : 2025-03-01Epub Date: 2024-07-02DOI: 10.1016/j.tcb.2024.06.003
Alessio Butera, Ivano Amelio
{"title":"Deciphering the significance of p53 mutant proteins.","authors":"Alessio Butera, Ivano Amelio","doi":"10.1016/j.tcb.2024.06.003","DOIUrl":"10.1016/j.tcb.2024.06.003","url":null,"abstract":"<p><p>Mutations in the p53 gene compromise its role as guardian of genomic integrity, yielding predominantly missense p53 mutant proteins. The gain-of-function hypothesis has long suggested that these mutant proteins acquire new oncogenic properties; however, recent studies challenge this notion, indicating that targeting these mutants may not impact the fitness of cancer cells. Mounting evidence indicates that tumorigenesis involves a cooperative interplay between driver mutations and cellular state, influenced by developmental stage, external insults, and tissue damage. Consistently, the behavior and properties of p53 mutants are altered by the context. This article aims to provide a balanced summary of the evolving evidence regarding the contribution of p53 mutants in the biology of cancer while contemplating alternative frameworks to decipher the complexity of p53 mutants within their physiological contexts.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"258-268"},"PeriodicalIF":13.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Trends in Cell BiologyPub Date : 2025-03-01Epub Date: 2025-01-21DOI: 10.1016/j.tcb.2025.01.001
Pablo Lanuza-Gracia, Jonas Juan-Mateu, Juan Valcárcel
{"title":"Splice age: mTORC1-mediated RNA splicing in metabolism and ageing.","authors":"Pablo Lanuza-Gracia, Jonas Juan-Mateu, Juan Valcárcel","doi":"10.1016/j.tcb.2025.01.001","DOIUrl":"10.1016/j.tcb.2025.01.001","url":null,"abstract":"<p><p>The target of rapamycin complex mTORC1 has key roles in cell growth and metabolism and its inhibition delays ageing. Recent work by Ogawa et al. in Caenorhabditis elegans argues that modulation of pre-mRNA splicing factors and alternative splicing are key mediators of mTORC1 signalling and can enhance longevity.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"183-185"},"PeriodicalIF":13.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Trends in Cell BiologyPub Date : 2025-03-01Epub Date: 2025-02-20DOI: 10.1016/j.tcb.2025.02.001
Zhiying Yao, Ziqiu Wang, Peiguo Yang
{"title":"The G3BP1 RNP complex at focal adhesion tunes cell migration.","authors":"Zhiying Yao, Ziqiu Wang, Peiguo Yang","doi":"10.1016/j.tcb.2025.02.001","DOIUrl":"10.1016/j.tcb.2025.02.001","url":null,"abstract":"<p><p>Ribonucleoprotein (RNP) complexes can form multiple mesoscale assemblies, including stress granules (SGs). However, the function and regulation of the soluble RNP complexes are not fully understood. A recent study by Boraas et al. showed that G3BP1, a key node in SG formation, forms focal adhesion (FA)-localized RNP complexes and regulates cell migration.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"180-182"},"PeriodicalIF":13.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Trends in Cell BiologyPub Date : 2025-03-01Epub Date: 2025-01-14DOI: 10.1016/j.tcb.2024.12.008
Alba Seguí-Pérez, Raquel Castillo-González, Lucía Sancho-Temiño, Aránzazu Cruz-Adalia
{"title":"Newly identified cell types crucial for gut commensal tolerance.","authors":"Alba Seguí-Pérez, Raquel Castillo-González, Lucía Sancho-Temiño, Aránzazu Cruz-Adalia","doi":"10.1016/j.tcb.2024.12.008","DOIUrl":"10.1016/j.tcb.2024.12.008","url":null,"abstract":"<p><p>The generation of regulatory T cells (Tregs) through interactions with antigen-presenting cells (APCs) is essential for establishing tolerance to gut commensals. Recent findings highlight the critical role of RORγt-lineage APCs, especially in gut-associated lymphoid tissues, in the induction of microbiota-specific peripheral Tregs and maintaining gut immune homeostasis.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"186-189"},"PeriodicalIF":13.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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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