{"title":"Metabolism and mRNA translation: a nexus of cancer plasticity.","authors":"Xinpu Tang, Kaixiu Li, Yuqing Wang, Stéphane Rocchi, Shensi Shen, Michael Cerezo","doi":"10.1016/j.tcb.2024.10.009","DOIUrl":"https://doi.org/10.1016/j.tcb.2024.10.009","url":null,"abstract":"<p><p>Tumors often face energy deprivation due to mutations, hypoxia, and nutritional deficiencies within the harsh tumor microenvironment (TME), and as an effect of anticancer treatments. This metabolic stress triggers adaptive reprogramming of mRNA translation, which in turn adjusts metabolic plasticity and associated signaling pathways to ensure tumor cell survival. Emerging evidence is beginning to reveal the complex interplay between metabolism and mRNA translation, shedding light on the mechanisms that synchronize ribosome assembly and reconfigure translation programs under metabolic stress. This review explores recent advances in our understanding of the coordination between metabolism and mRNA translation, offering insights that could inform therapeutic strategies targeting both cancer metabolism and translation, with the aim of disrupting cancer cell plasticity and survival.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741543","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":"Targeting SHP1 and SHP2 to suppress tumors and enhance immunosurveillance.","authors":"Yijun Zhao, Linjia Jiang","doi":"10.1016/j.tcb.2024.10.008","DOIUrl":"https://doi.org/10.1016/j.tcb.2024.10.008","url":null,"abstract":"<p><p>The nonreceptor tyrosine phosphatases (PTPS) SHP1 and SHP2 have crucial roles in dephosphorylating an array of substrates involved in pathways comprising receptor tyrosine kinases (RTKs) and immune receptors. This regulation maintains a delicate balance between the activation and inhibition of signal transduction, ensuring appropriate biological outcomes. In this review, we summarize research focused on elucidating the functions of SHP1 and SHP2 in hematopoiesis, immune regulation, and tumor biology, emphasizing recent findings related to cancer-driven immune evasion. Furthermore, we highlight the significant effects of SHP1 and SHP2 inhibitors in enhancing cancer treatment, specifically through the facilitation of chemotherapy and augmentation of immune activation.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693812","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":"Central role of the ER proteostasis network in healthy aging.","authors":"Claudio Hetz, Andrew Dillin","doi":"10.1016/j.tcb.2024.10.003","DOIUrl":"https://doi.org/10.1016/j.tcb.2024.10.003","url":null,"abstract":"<p><p>Aging trajectories vary among individuals, characterized by progressive functional decline, often leading to disease states. One of the central hallmarks of aging is the deterioration of proteostasis, where the function of the endoplasmic reticulum (ER) is dramatically affected. ER stress is monitored and adjusted by the unfolded protein response (UPR); a signaling pathway that mediates adaptive processes to restore proteostasis. Studies in multiple model organisms (yeast, worms, flies, and mice) in addition to human tissue indicates that adaptive UPR signaling contributes to healthy aging. Strategies to improve ER proteostasis using small molecules and gene therapy reduce the decline of organ function during normal aging in mammals. This article reviews recent advances in understanding the significance of the ER proteostasis network to normal aging and its relationship with other hallmarks of aging such as senescence.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640336","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}
Can Pan, Xueping Wang, Chuan Yang, Kai Fu, Fang Wang, Liwu Fu
{"title":"The culture and application of circulating tumor cell-derived organoids.","authors":"Can Pan, Xueping Wang, Chuan Yang, Kai Fu, Fang Wang, Liwu Fu","doi":"10.1016/j.tcb.2024.10.004","DOIUrl":"https://doi.org/10.1016/j.tcb.2024.10.004","url":null,"abstract":"<p><p>Circulating tumor cells (CTCs), which have the heterogeneity and histological properties of the primary tumor and metastases, are shed from the primary tumor and/or metastatic lesions into the vasculature and initiate metastases at remote sites. In the clinic, CTCs are used extensively in liquid biopsies for early screening, diagnosis, treatment, and prognosis. Current research focuses on using CTC-derived models to study tumor heterogeneity and metastasis, with 3D organoids emerging as a promising tool in cancer research and precision oncology. However, isolating and enriching CTCs from blood remains challenging due to their scarcity, exacerbated by the lack of an optimized culture medium for CTC-derived organoids (CTCDOs). In this review, we summarize the origin, isolation, enrichment, culture, validation, and clinical application of CTCs and CTCDOs.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633160","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":"Emerging roles of palmitoylation in pyroptosis.","authors":"Na Zhang, Yuanxin Yang, Daichao Xu","doi":"10.1016/j.tcb.2024.10.005","DOIUrl":"https://doi.org/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":""},"PeriodicalIF":13.0,"publicationDate":"2024-11-08","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}
{"title":"MDM4 exon skipping upon dysfunctional ribosome assembly.","authors":"Jennifer Jansen, Matthias Dobbelstein","doi":"10.1016/j.tcb.2024.10.006","DOIUrl":"https://doi.org/10.1016/j.tcb.2024.10.006","url":null,"abstract":"<p><p>Recent studies revealed how nucleolar stress enhances MDM4 exon skipping and activates p53 via the ribosomal protein L22 (RPL22; eL22). Tumor-associated L22 mutations lead to full-length MDM4 synthesis, overcoming tumor suppression by p53. This forum article explores how MDM4 splicing patterns integrate stress signaling to take p53-dependent cell fate decisions.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633158","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":"Dynamic rRNA modifications as a source of ribosome heterogeneity.","authors":"Ivan Milenkovic, Eva Maria Novoa","doi":"10.1016/j.tcb.2024.10.001","DOIUrl":"https://doi.org/10.1016/j.tcb.2024.10.001","url":null,"abstract":"<p><p>Ribosomal RNAs (rRNA) are the most abundant RNA molecules in almost all cell types. The general consensus in the field is that rRNA modifications are largely species-specific, with most previous works and databases solely stratifying modifications by the species of origin, without taking other levels of complexity into account. However, new evidence has emerged suggesting dynamic rRNA modifications may have additional layers of complexity and might play an important role in development and disease. In this review article, we summarize recent evidence supporting heterogeneity and dynamics in rRNA modifications in diverse biological contexts, challenging the simplistic view of 'one-species-one-rRNA-modification-pattern'. Moreover, we highlight how rRNA modification dynamics have been studied to date and how long-read sequencing methods can significantly improve our understanding of this largely unexplored yet highly abundant RNA family, across tissues, developmental stages, and diseases.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585245","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 : 2024-11-01Epub Date: 2024-05-21DOI: 10.1016/j.tcb.2024.03.007
Hope E Merens, Karine Choquet, Autum R Baxter-Koenigs, L Stirling Churchman
{"title":"Timing is everything: advances in quantifying splicing kinetics.","authors":"Hope E Merens, Karine Choquet, Autum R Baxter-Koenigs, L Stirling Churchman","doi":"10.1016/j.tcb.2024.03.007","DOIUrl":"10.1016/j.tcb.2024.03.007","url":null,"abstract":"<p><p>Splicing is a highly regulated process critical for proper pre-mRNA maturation and the maintenance of a healthy cellular environment. Splicing events are impacted by ongoing transcription, neighboring splicing events, and cis and trans regulatory factors on the respective pre-mRNA transcript. Within this complex regulatory environment, splicing kinetics have the potential to influence splicing outcomes but have historically been challenging to study in vivo. In this review, we highlight recent technological advancements that have enabled measurements of global splicing kinetics and of the variability of splicing kinetics at single introns. We demonstrate how identifying features that are correlated with splicing kinetics has increased our ability to form potential models for how splicing kinetics may be regulated in vivo.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"968-981"},"PeriodicalIF":13.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081871","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 : 2024-11-01Epub Date: 2024-10-07DOI: 10.1016/j.tcb.2024.09.002
Chenghao Yan, Xu Liu, Haodong Xu, Liming Wang
{"title":"Cytoplasmic mtDNA clearance suppresses inflammatory immune responses.","authors":"Chenghao Yan, Xu Liu, Haodong Xu, Liming Wang","doi":"10.1016/j.tcb.2024.09.002","DOIUrl":"10.1016/j.tcb.2024.09.002","url":null,"abstract":"<p><p>Upon various stresses, mtDNA leaks from mitochondria into the cytoplasm, leading to cellular dysfunction and inflammation, thereby exacerbating disease progression. The autophagy-lysosome pathway has emerged as a pivotal quality control mechanism for eliminating abnormal cytoplasmic mtDNA. This article summarizes the mechanisms underlying mtDNA-triggered inflammation and how cytoplasmic mtDNA is eliminated.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"897-900"},"PeriodicalIF":13.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395611","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 : 2024-11-01Epub Date: 2024-02-10DOI: 10.1016/j.tcb.2024.01.004
Julian Schwärzler, Lisa Mayr, Felix Grabherr, Herbert Tilg, Timon E Adolph
{"title":"Epithelial metabolism as a rheostat for intestinal inflammation and malignancy.","authors":"Julian Schwärzler, Lisa Mayr, Felix Grabherr, Herbert Tilg, Timon E Adolph","doi":"10.1016/j.tcb.2024.01.004","DOIUrl":"10.1016/j.tcb.2024.01.004","url":null,"abstract":"<p><p>The gut epithelium protects the host from a potentially hostile environment while allowing nutrient uptake that is vital for the organism. To maintain this delicate task, the gut epithelium has evolved multilayered cellular functions ranging from mucus production to hormone release and orchestration of mucosal immunity. Here, we review the execution of intestinal epithelial metabolism in health and illustrate how perturbation of epithelial metabolism affects experimental gut inflammation and tumorigenesis. We also discuss the impact of environmental factors and host-microbe interactions on epithelial metabolism in the context of inflammatory bowel disease and colorectal cancer. Insights into epithelial metabolism hold promise to unravel mechanisms of organismal health that may be therapeutically exploited in humans in the future.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"913-927"},"PeriodicalIF":13.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139716632","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}