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New twist on BRCA1-mediated DNA recombination repair and tumor suppression. brca1介导的DNA重组修复和肿瘤抑制的新进展。
IF 18.1 1区 生物学
Trends in Cell Biology Pub Date : 2025-06-05 DOI: 10.1016/j.tcb.2025.05.002
Dali Zong, Raphael Pavani, André Nussenzweig
{"title":"New twist on BRCA1-mediated DNA recombination repair and tumor suppression.","authors":"Dali Zong, Raphael Pavani, André Nussenzweig","doi":"10.1016/j.tcb.2025.05.002","DOIUrl":"10.1016/j.tcb.2025.05.002","url":null,"abstract":"<p><p>Ever since BRCA1 germline mutations were found to confer a strong predisposition to the development of breast and ovarian cancers, there has been great interest in determining how this protein suppresses tumor formation. Through more than two decades of research, it has become clear that BRCA1 safeguards our genome mainly by promoting DNA repair through homologous recombination (HR). This opinion article outlines our evolving view of BRCA1's role in end resection, an upstream commitment step for HR, and highlights recent discoveries suggesting that the context in which DNA breaks are generated dictates whether BRCA1 is required for end resection. In addition, strong emerging evidence for the tumor-suppressive function of BRCA1 being mediated predominantly by its indispensable role in supporting RAD51-dependent recombination downstream of end resection is discussed.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":""},"PeriodicalIF":18.1,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12354295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Emerging roles of palmitoylation in pyroptosis. 棕榈酰化在高温变态反应中的新作用。
IF 13 1区 生物学
Trends in Cell Biology Pub Date : 2025-06-01 Epub Date: 2024-11-08 DOI: 10.1016/j.tcb.2024.10.005
Na Zhang, Yuanxin Yang, Daichao Xu
{"title":"Emerging roles of palmitoylation in pyroptosis.","authors":"Na Zhang, Yuanxin Yang, Daichao Xu","doi":"10.1016/j.tcb.2024.10.005","DOIUrl":"10.1016/j.tcb.2024.10.005","url":null,"abstract":"<p><p>Pyroptosis is a lytic, proinflammatory type of programmed cell death crucial for the immune response to pathogen infections and internal danger signals. Gasdermin D (GSDMD) acts as the pore-forming protein in pyroptosis following inflammasome activation. While recent research has improved our understanding of pyroptosis activation and execution, many aspects regarding the molecular mechanisms controlling inflammasome and GSDMD activation remain to be elucidated. A growing body of literature has shown that S-palmitoylation, a reversible post-translational modification (PTM) that attaches palmitate to cysteine residues, contributes to multi-layered regulation of pyroptosis. This review summarizes the emerging roles of S-palmitoylation in pyroptosis research with a focus on mechanisms that regulate NLRP3 inflammasome and GSDMD activation.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"500-514"},"PeriodicalIF":13.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633146","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}
引用次数: 0
Phenotypic analysis of complex bioengineered 3D models. 复杂生物工程3D模型的表型分析。
IF 13 1区 生物学
Trends in Cell Biology Pub Date : 2025-06-01 Epub Date: 2025-01-09 DOI: 10.1016/j.tcb.2024.12.004
Akhilandeshwari Ravichandran, Vaibhav Mahajan, Tom van de Kemp, Anna Taubenberger, Laura J Bray
{"title":"Phenotypic analysis of complex bioengineered 3D models.","authors":"Akhilandeshwari Ravichandran, Vaibhav Mahajan, Tom van de Kemp, Anna Taubenberger, Laura J Bray","doi":"10.1016/j.tcb.2024.12.004","DOIUrl":"10.1016/j.tcb.2024.12.004","url":null,"abstract":"<p><p>With advances in underlying technologies such as complex multicellular systems, synthetic materials, and bioengineering techniques, we can now generate in vitro miniaturized human tissues that recapitulate the organotypic features of normal or diseased tissues. Importantly, these 3D culture models have increasingly provided experimental access to diverse and complex tissues architectures and their morphogenic assembly in vitro. This review presents an analytical toolbox for biological researchers using 3D modeling technologies through which they can find a collation of currently available methods to phenotypically assess their 3D models in their normal state as well as their response to therapeutic or pathological agents.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"470-482"},"PeriodicalIF":13.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967468","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}
引用次数: 0
Mapping the funding landscape for public engagement with science. 绘制公众参与科学的资助格局。
IF 13 1区 生物学
Trends in Cell Biology Pub Date : 2025-06-01 Epub Date: 2025-05-08 DOI: 10.1016/j.tcb.2025.04.001
Fanuel J Muindi
{"title":"Mapping the funding landscape for public engagement with science.","authors":"Fanuel J Muindi","doi":"10.1016/j.tcb.2025.04.001","DOIUrl":"10.1016/j.tcb.2025.04.001","url":null,"abstract":"<p><p>The funding landscape for public engagement with science (PES) is highly dynamic. More research is needed to better track and understand the rapidly evolving funding landscape in PES. This paper shares insights from an ongoing mapping of the funding landscape and offers recommendations for new research to improve the resolution of such maps.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"453-455"},"PeriodicalIF":13.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051135","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}
引用次数: 0
Centrosomes and cancer: balancing tumor-promoting and inhibitory roles. 中心体与癌症：平衡促肿瘤和抑制肿瘤的作用。
IF 13 1区 生物学
Trends in Cell Biology Pub Date : 2025-06-01 Epub Date: 2025-04-23 DOI: 10.1016/j.tcb.2025.02.009
Susana A Godinho, Renata Basto
{"title":"Centrosomes and cancer: balancing tumor-promoting and inhibitory roles.","authors":"Susana A Godinho, Renata Basto","doi":"10.1016/j.tcb.2025.02.009","DOIUrl":"10.1016/j.tcb.2025.02.009","url":null,"abstract":"<p><p>The centrosome duplicates only once per cell cycle such that, in preparation for mitosis, cells contain two centrosomes, allowing the formation of a bipolar spindle and segregation of chromosomes to the two daughter cells. Defects in centrosome numbers have long been recognized in human tumors and are postulated to be a driver of malignancy through chromosome instability. However, current work has revealed a multitude of phenotypes associated with amplified centrosomes beyond mitotic defects that may play a role in disease onset and progression, including cancer. This review focuses on the complexity of outcomes connected to centrosome abnormalities and the challenges that result from aberrant loss and gain of centrosome numbers. We discuss the tumor-promoting and inhibitory roles of amplified centrosomes, and propose that their impact on both physiology and disease is intrinsically linked to cellular context.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"515-526"},"PeriodicalIF":13.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053952","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}
引用次数: 0
Diverse routes to mitophagy governed by ubiquitylation and mitochondrial import. 由泛素化和线粒体输入控制的线粒体自噬的多种途径。
IF 13 1区 生物学
Trends in Cell Biology Pub Date : 2025-06-01 Epub Date: 2025-02-07 DOI: 10.1016/j.tcb.2025.01.003
Michael J Clague, Sylvie Urbé
{"title":"Diverse routes to mitophagy governed by ubiquitylation and mitochondrial import.","authors":"Michael J Clague, Sylvie Urbé","doi":"10.1016/j.tcb.2025.01.003","DOIUrl":"10.1016/j.tcb.2025.01.003","url":null,"abstract":"<p><p>The selective removal of mitochondria by mitophagy proceeds via multiple mechanisms and is essential for human well-being. The PINK1/Parkin and NIX/BNIP3 pathways are strongly linked to mitochondrial dysfunction and hypoxia, respectively. Both are regulated by ubiquitylation and mitochondrial import. Recent studies have elucidated how the ubiquitin kinase PINK1 acts as a sensor of mitochondrial import stress through stable interaction with a mitochondrial import supercomplex. The stability of BNIP3 and NIX is regulated by the SCF<sup>FBXL4</sup> ubiquitin ligase complex. Substrate recognition requires an adaptor molecule, PPTC7, whose availability is limited by mitochondrial import. Unravelling the functional implications of each mode of mitophagy remains a critical challenge. We propose that mitochondrial import stress prompts a switch between these two pathways.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"527-538"},"PeriodicalIF":13.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374991","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}
引用次数: 0
Hypoxia-specific transcriptional condensates drive metastasis. 缺氧特异性转录凝聚物驱动转移。
IF 18.1 1区 生物学
Trends in Cell Biology Pub Date : 2025-06-01 Epub Date: 2025-05-16 DOI: 10.1016/j.tcb.2025.04.008
Steven Ingersoll, Xiaojun Ren
{"title":"Hypoxia-specific transcriptional condensates drive metastasis.","authors":"Steven Ingersoll, Xiaojun Ren","doi":"10.1016/j.tcb.2025.04.008","DOIUrl":"10.1016/j.tcb.2025.04.008","url":null,"abstract":"<p><p>Compartmentalization by phase separation is an emerging principle for regulating transcription. While the compartmentalization mechanisms by which cells regulate genetic activities in response to specific environmental signals remain largely unclear, a recent study by Gao et al. suggests that hypoxia induces the formation of phase-separated condensates, which impacts metastasis-related transcription through chromatin organization.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"456-458"},"PeriodicalIF":18.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12410693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Modulating cell-free DNA biology as the next frontier in liquid biopsies. 调节无细胞DNA生物学是液体活检的下一个前沿。
IF 13 1区 生物学
Trends in Cell Biology Pub Date : 2025-06-01 Epub Date: 2024-12-26 DOI: 10.1016/j.tcb.2024.11.007
Shervin Tabrizi, Carmen Martin-Alonso, Kan Xiong, Sangeeta N Bhatia, Viktor A Adalsteinsson, J Christopher Love
{"title":"Modulating cell-free DNA biology as the next frontier in liquid biopsies.","authors":"Shervin Tabrizi, Carmen Martin-Alonso, Kan Xiong, Sangeeta N Bhatia, Viktor A Adalsteinsson, J Christopher Love","doi":"10.1016/j.tcb.2024.11.007","DOIUrl":"10.1016/j.tcb.2024.11.007","url":null,"abstract":"<p><p>Technical advances over the past two decades have enabled robust detection of cell-free DNA (cfDNA) in biological samples. Yet, higher clinical sensitivity is required to realize the full potential of liquid biopsies. This opinion article argues that to overcome current limitations, the abundance of informative cfDNA molecules - such as circulating tumor DNA (ctDNA) - collected in a sample needs to increase. To accomplish this, new methods to modulate the biological processes that govern cfDNA production, trafficking, and clearance in the body are needed, informed by a deeper understanding of cfDNA biology. Successful development of such methods could enable a major leap in the performance of liquid biopsies and vastly expand their utility across the spectrum of clinical care.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"459-469"},"PeriodicalIF":13.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Emerging approaches to enhance human brain organoid physiology. 增强人脑类器官生理学的新方法。
IF 13 1区 生物学
Trends in Cell Biology Pub Date : 2025-06-01 Epub Date: 2025-01-17 DOI: 10.1016/j.tcb.2024.12.001
Anna Pagliaro, Benedetta Artegiani, Delilah Hendriks
{"title":"Emerging approaches to enhance human brain organoid physiology.","authors":"Anna Pagliaro, Benedetta Artegiani, Delilah Hendriks","doi":"10.1016/j.tcb.2024.12.001","DOIUrl":"10.1016/j.tcb.2024.12.001","url":null,"abstract":"<p><p>Brain organoids are important 3D models for studying human brain development, disease, and evolution. To overcome some of the existing limitations that affect organoid quality, reproducibility, characteristics, and in vivo resemblance, current efforts are directed to improve their physiological relevance by exploring different, yet interconnected, routes. In this review, these approaches and their latest developments are discussed, including stem cell optimization, refining morphogen administration strategies, altering the extracellular matrix (ECM) niche, and manipulating tissue architecture to mimic in vivo brain morphogenesis. Additionally, strategies to increase cell diversity and enhance organoid maturation, such as establishing co-cultures, assembloids, and organoid in vivo xenotransplantation, are reviewed. We explore how these various factors can be tuned and intermingled and speculate on future avenues towards even more physiologically-advanced brain organoids.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"483-499"},"PeriodicalIF":13.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017020","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}
引用次数: 0
Tumor-stromal metabolic crosstalk in pancreatic cancer. 胰腺癌的肿瘤-间质代谢串扰。
IF 18.1 1区 生物学
Trends in Cell Biology Pub Date : 2025-05-26 DOI: 10.1016/j.tcb.2025.04.007
Ravi Thakur, Nicholas J Mullen, Kamiya Mehla, Pankaj K Singh
{"title":"Tumor-stromal metabolic crosstalk in pancreatic cancer.","authors":"Ravi Thakur, Nicholas J Mullen, Kamiya Mehla, Pankaj K Singh","doi":"10.1016/j.tcb.2025.04.007","DOIUrl":"10.1016/j.tcb.2025.04.007","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a dire prognosis. Standard-of-care chemotherapy regimens offer marginal survival benefit and carry risk of severe toxicity, while immunotherapy approaches have uniformly failed in clinical trials. Extensive desmoplasia in the PDAC tumor microenvironment (TME) disrupts blood flow to and from the tumor, thereby creating a nutrient-depleted, hypoxic, and acidic milieu that suppresses the function of antitumor immune cells and imparts chemotherapy resistance. Additionally, recent seminal studies have demonstrated crucial roles for metabolic crosstalk - the exchange of metabolites between PDAC cells and stromal cell populations in the TME - in establishing and maintaining core malignant behaviors of PDAC: tumor growth, metastasis, immune evasion, and therapy resistance. In this review, we provide a conceptual overview of metabolic crosstalk and how it evolves under various selection pressures in the TME, analyze the landscape of proposed tumorigenic metabolic crosstalk pathways, and highlight potentially druggable nodes.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":""},"PeriodicalIF":18.1,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12353458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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