Signal Transduction and Targeted Therapy最新文献

{"title":"Spatiotemporal transcriptomics elucidates the pathogenesis of fulminant viral myocarditis","authors":"Huihui Li, Xueting Chen, James Jiqi Wang, Juan Shen, Kudusi Abuduwufuer, Zhao Zhang, Zhensheng Dong, Zheng Wen, Jingwei He, Silian Chen, Wanshun Li, Chen Chen, Fan Li, Xiaodong Fang, Dao Wen Wang","doi":"10.1038/s41392-025-02143-9","DOIUrl":"https://doi.org/10.1038/s41392-025-02143-9","url":null,"abstract":"<p>Fulminant myocarditis (FM) is a severe inflammatory condition of the myocardium that often results in sudden death, particularly in young individuals. In this study, we employed single-nucleus and spatial transcriptomics to perform a comprehensive analysis of coxsackievirus B3 (CVB3)-induced FM in A/J mice, spanning seven distinct time points pre- and post-treatment. Our findings reveal that mesothelial cells play a critical role in the early stage of myocarditis by acting as primary targets for CVB3 infection. This triggers the activation of macrophages, initiating a cascade of inflammation. Subsequently, pro-inflammatory Inflammatory_Mac and T cells infiltrate the myocardium, driving tissue damage. We also identified Cd8⁺ effector T cells as key mediators of cardiomyocyte injury. These cells release cytotoxic molecules, particularly IFN-γ, which modulates the expression of <i>Spi1</i>, a factor implicated in exacerbating cardiomyocyte death and amplifying disease progression. Therapeutic interventions targeting the IFN-γ/<i>Spi1</i> axis demonstrated significant efficacy in FM models. Notably, intravenous immunoglobulin (IVIG) treatment reduced mortality, suppressed viral proliferation, and mitigated the hyperinflammatory state of FM. IVIG therapy also downregulated IFN-γ and <i>Spi1</i> expression, underscoring its immunomodulatory and therapeutic potential. This comprehensive spatiotemporal transcriptomic analysis provides profound insights into the pathogenesis of FM and highlights actionable therapeutic targets, paving the way for more effective management strategies for this life-threatening condition.</p>","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"12 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Src inhibition potentiates MCL-1 antagonist activity in acute myeloid leukemia","authors":"Xiaoyan Hu, Lin Li, Jewel Nkwocha, Maciej Kmieciak, Shengzhe Shang, L. Ashley Cowart, Yang Yue, Katsuhisa Horimoto, Adam Hawkridge, Arjun Rijal, Adolfo G. Mauro, Fadi N. Salloum, Lori Hazlehurst, Konstantinos Sdrimas, Zackary Moore, Liang Zhou, Gordon D. Ginder, Steven Grant","doi":"10.1038/s41392-025-02125-x","DOIUrl":"https://doi.org/10.1038/s41392-025-02125-x","url":null,"abstract":"<p>The importance of MCL-1 in leukemogenesis has prompted development of MCL-1 antagonists e.g., S63845, MIK665. However, their effectiveness in acute myeloid leukemia (AML) is limited by compensatory MCL-1 accumulation via the ubiquitin proteasome system. Here, we investigated mechanisms by which kinase inhibitors with Src inhibitory activity e.g., bosutinib (SKI-606) might circumvent this phenomenon. MCL-1 antagonist/SKI-606 co-administration synergistically induced apoptosis in diverse AML cell lines. Consistently, Src or MCL-1 knockdown with shRNA markedly sensitized cells to MCL-1 inhibitors or SKI-606 respectively, while ectopic MCL-1 expression significantly diminished apoptosis. Mechanistically, MCL-1 antagonist exposure induced MCL-1 up-regulation, an event blocked by Src inhibitors or Src shRNA knock-down. MCL-1 down-regulation was associated with diminished transcription and increased K48-linked degradative ubiquitination. Enhanced cell death depended functionally upon down-regulation of phosphorylated STAT3 (Tyr705/Ser727) and cytoprotective downstream targets c-Myc and BCL-xL, as well as BAX/BAK activation, and NOXA induction. Importantly, the Src/MCL-1 inhibitor regimen robustly killed primary AML cells, including primitive progenitors, but spared normal hematopoietic CD34⁺ cells and human cardiomyocytes. Notably, the regimen significantly improved survival in an MV4-11 cell xenograft model, while reducing tumor burden in two patient-derived xenograft (PDX) AML models and increased survival in a third. These findings argue that Src inhibitors such as SKI-606 potentiate MCL-1 antagonist anti-leukemic activity in vitro and in vivo by blocking MCL-1 antagonist-mediated cytoprotective MCL-1 accumulation by promoting degradative ubiquitination, disrupting STAT-3-mediated transcription, and inducing NOXA-mediated MCL-1 degradation. They also suggest that this strategy may improve MCL-1 antagonist efficacy in AML and potentially other malignancies.</p>","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"63 3 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics","authors":"Xiao Ma, Tengda Huang, Xiangzheng Chen, Qian Li, Mingheng Liao, Li Fu, Jiwei Huang, Kefei Yuan, Zhen Wang, Yong Zeng","doi":"10.1038/s41392-024-02104-8","DOIUrl":"https://doi.org/10.1038/s41392-024-02104-8","url":null,"abstract":"<p>Liver repair and regeneration are crucial physiological responses to hepatic injury and are orchestrated through intricate cellular and molecular networks. This review systematically delineates advancements in the field, emphasizing the essential roles played by diverse liver cell types. Their coordinated actions, supported by complex crosstalk within the liver microenvironment, are pivotal to enhancing regenerative outcomes. Recent molecular investigations have elucidated key signaling pathways involved in liver injury and regeneration. Viewed through the lens of metabolic reprogramming, these pathways highlight how shifts in glucose, lipid, and amino acid metabolism support the cellular functions essential for liver repair and regeneration. An analysis of regenerative variability across pathological states reveals how disease conditions influence these dynamics, guiding the development of novel therapeutic strategies and advanced techniques to enhance liver repair and regeneration. Bridging laboratory findings with practical applications, recent clinical trials highlight the potential of optimizing liver regeneration strategies. These trials offer valuable insights into the effectiveness of novel therapies and underscore significant progress in translational research. In conclusion, this review intricately links molecular insights to therapeutic frontiers, systematically charting the trajectory from fundamental physiological mechanisms to innovative clinical applications in liver repair and regeneration.</p>","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"207 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143367362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatocellular carcinoma: signaling pathways and therapeutic advances","authors":"Jiaojiao Zheng, Siying Wang, Lei Xia, Zhen Sun, Kui Ming Chan, René Bernards, Wenxin Qin, Jinhong Chen, Qiang Xia, Haojie Jin","doi":"10.1038/s41392-024-02075-w","DOIUrl":"https://doi.org/10.1038/s41392-024-02075-w","url":null,"abstract":"<p>Liver cancer represents a major global health concern, with projections indicating that the number of new cases could surpass 1 million annually by 2025. Hepatocellular carcinoma (HCC) constitutes around 90% of liver cancer cases and is primarily linked to factors incluidng aflatoxin, hepatitis B (HBV) and C (HCV), and metabolic disorders. There are no obvious symptoms in the early stage of HCC, which often leads to delays in diagnosis. Therefore, HCC patients usually present with tumors in advanced and incurable stages. Several signaling pathways are dis-regulated in HCC and cause uncontrolled cell propagation, metastasis, and recurrence of HCC. Beyond the frequently altered and therapeutically targeted receptor tyrosine kinase (RTK) pathways in HCC, pathways involved in cell differentiation, telomere regulation, epigenetic modification and stress response also provide therapeutic potential. Investigating the key signaling pathways and their inhibitors is pivotal for achieving therapeutic advancements in the management of HCC. At present, the primary therapeutic approaches for advanced HCC are tyrosine kinase inhibitors (TKI), immune checkpoint inhibitors (ICI), and combination regimens. New trials are investigating combination therapies involving ICIs and TKIs or anti-VEGF (endothelial growth factor) therapies, as well as combinations of two immunotherapy regimens. The outcomes of these trials are expected to revolutionize HCC management across all stages. Here, we provide here a comprehensive review of cellular signaling pathways, their therapeutic potential, evidence derived from late-stage clinical trials in HCC and discuss the concepts underlying earlier clinical trials, biomarker identification, and the development of more effective therapeutics for HCC.</p>","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"139 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143258038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoadjuvant apatinib addition to sintilimab and carboplatin-taxane based chemotherapy in patients with early triple-negative breast cancer: the phase 2 NeoSAC trial","authors":"Guoshuang Shen, Zhilin Liu, Miaozhou Wang, Yi Zhao, Xinlan Liu, Yujin Hou, Wenbiao Ma, Jingqi Han, Xiaofeng Zhou, Dengfeng Ren, Fuxing Zhao, Zitao Li, Shifen Huang, Yongzhi Chen, Yingjian He, Yan Liu, Zijun Zhu, Yongxin Li, Jinming Li, Mengting Da, Hongnan Mo, Feng Du, Liang Cui, Jing Bai, Zhen Liu, Fei Ma, Jiuda Zhao","doi":"10.1038/s41392-025-02137-7","DOIUrl":"https://doi.org/10.1038/s41392-025-02137-7","url":null,"abstract":"<p>We aimed to evaluate the efficacy and safety of adding apatinib, to sintilimab and chemotherapy in the neoadjuvant treatment of early triple-negative breast cancer (TNBC). In the phase 2 NeoSAC trial, patients with early TNBC received six cycles of apatinib, sintilimab, nab-paclitaxel, and carboplatin followed by surgery. The primary endpoint was pathological complete response (pCR) rate. Specimens collected pre-neoadjuvant therapy and post-surgery were retained for comprehensive analysis of predictive biomarkers and the impact on the tumor microenvironment. Among 34 enrolled patients, 24 achieved pCR (70.6%; 95% confidence interval (CI), 53.0-85.3), and 79.4% (95% CI, 65.1-93.7) had residual cancer burden 0-I. Imaging evaluation showed 21 complete responses (61.8%) and 13 partial responses (38.2%). The most common grade 3-4 adverse events were leukopenia (47%), neutropenia (36%), and thrombocytopenia (24%). The 36-month disease-free survival rate stood at 94.1% with a median follow-up of 39.1 months. Notably, baseline high ImmuneScore, immune cell infiltration, and enrichment of interferon-related pathways correlated with pCR. Comparison of pre-neoadjuvant and post-surgery data revealed that the pCR group treated with this novel regimen exhibited an upregulation of distinct immune cell subsets, thereby activating the tumor microenvironment. Moreover, higher oxeiptosis scores were associated with an increased likelihood of achieving pCR. Following neoadjuvant therapy, the pCR group showed a decrease in oxeiptosis score, whereas the non-pCR group exhibited an increase. Our study suggests that apatinib, sintilimab combined with carboplatin and nab-paclitaxel chemotherapy showed a promising clinical activity and manageable safety profile in early TNBC and merits further study. ClinicalTrials.gov registration: NCT04722718.</p>","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"11 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143258037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial heterogeneity: subpopulations with distinct metabolic activities","authors":"Fabian den Brave, Swadha Mishra, Thomas Becker","doi":"10.1038/s41392-025-02130-0","DOIUrl":"https://doi.org/10.1038/s41392-025-02130-0","url":null,"abstract":"<p>In a recent study published in <i>Nature</i>, Ryu et al.¹ demonstrate the presence of metabolically distinct mitochondrial subpopulations within one cell. One mitochondrial subpopulation contains the F₁F_O-ATP synthase for oxidative phosphorylation (OXPHOS), while a second population performs reductive biosynthesis of proline and ornithine. The separation of mitochondria into two functionally distinct pools is reversible and depends on their fusion and fission.</p>","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"40 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143258036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liver diseases: epidemiology, causes, trends and predictions","authors":"Can Gan, Yuan Yuan, Haiyuan Shen, Jinhang Gao, Xiangxin Kong, Zhaodi Che, Yangkun Guo, Hua Wang, Erdan Dong, Jia Xiao","doi":"10.1038/s41392-024-02072-z","DOIUrl":"https://doi.org/10.1038/s41392-024-02072-z","url":null,"abstract":"<p>As a highly complex organ with digestive, endocrine, and immune-regulatory functions, the liver is pivotal in maintaining physiological homeostasis through its roles in metabolism, detoxification, and immune response. Various factors including viruses, alcohol, metabolites, toxins, and other pathogenic agents can compromise liver function, leading to acute or chronic injury that may progress to end-stage liver diseases. While sharing common features, liver diseases exhibit distinct pathophysiological, clinical, and therapeutic profiles. Currently, liver diseases contribute to approximately 2 million deaths globally each year, imposing significant economic and social burdens worldwide. However, there is no cure for many kinds of liver diseases, partly due to a lack of thorough understanding of the development of these liver diseases. Therefore, this review provides a comprehensive examination of the epidemiology and characteristics of liver diseases, covering a spectrum from acute and chronic conditions to end-stage manifestations. We also highlight the multifaceted mechanisms underlying the initiation and progression of liver diseases, spanning molecular and cellular levels to organ networks. Additionally, this review offers updates on innovative diagnostic techniques, current treatments, and potential therapeutic targets presently under clinical evaluation. Recent advances in understanding the pathogenesis of liver diseases hold critical implications and translational value for the development of novel therapeutic strategies.</p>","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"21 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perioperative tislelizumab plus chemotherapy for locally advanced gastroesophageal junction adenocarcinoma (NEOSUMMIT-03): a prospective, nonrandomized, open-label, phase 2 trial","authors":"Run-Cong Nie, Shu-Qiang Yuan, Ya Ding, Yong-Ming Chen, Yuan-Fang Li, Cheng-Cai Liang, Mu-Yan Cai, Guo-Ming Chen, Wei Wang, Xiao-Wei Sun, De-Sheng Weng, Dan-Dan Li, Jing-Jing Zhao, Xiao-Jiang Chen, Yuan-Xiang Guan, Zhi-Min Liu, Yao Liang, Ma Luo, Jun Chi, Hai-Bo Qiu, Zhi-Wei Zhou, Xiao-Shi Zhang, Ying-Bo Chen","doi":"10.1038/s41392-025-02160-8","DOIUrl":"https://doi.org/10.1038/s41392-025-02160-8","url":null,"abstract":"<p>This prospective, nonrandomized, open-label phase 2 trial (Chinese Clinical Trial Registry, ChiCTR2200061906) aimed to evaluate the effectiveness of adding the PD-1 antibody tislelizumab to perioperative chemotherapy in patients with locally advanced gastroesophageal junction adenocarcinoma (GEJA). This study enrolled patients with GEJA clinically staged as cT3-4aNanyM0 or cT1-2N+M0 from October 2022 to June 2023. Eligible patients were administered three preoperative and five postoperative 3-week cycles of treatment with PD-1 antibody tislelizumab plus SOX (S-1 and oxaliplatin) regimen. The primary endpoint was major pathological response (MPR) rate. Thirty-two patients were enrolled. The median age was 60 years (range: 28–74 years), and 53.1% (17/32) patients were Siewert III type. All patients received at least one cycle of assigned preoperative treatment, and 93.8% (30/32) patients completed three cycles of assigned preoperative tislelizumab and SOX. The R0 resection rate was 96.9% (31/32). MPR, pathological complete response (pCR) of primary tumors and ypT0N0 rates were 50.0% (16/32, 95% CI: 31.9–68.1%), 28.1% (9/32, 95% CI: 13.7–46.7%) and 25.0% (8/32, 95% CI: 11.5–43.4%), respectively. The surgical morbidity rate was 15.6% (5/32), and no 30-day mortality was observed. In the preoperative and postoperative treatment periods, the rate of treatment-related grade 3–4 adverse events was 31.2% (10/32). At the date of 7^th Jan 2025, 8 (25.0%) patients occurred recurrence. Therefore, perioperative tislelizumab plus chemotherapy demonstrated significantly improved pathological regression and might be a promising option for patients with locally advanced resectable GEJA.</p>","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"90 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell transcriptomics reveals novel chondrocyte and osteoblast subtypes and their role in knee osteoarthritis pathogenesis","authors":"Yuan Liu, Wacili Da, Ming-Jie Xu, Chao-Xin Xiao, Tao Deng, Sheng-Liang Zhou, Xiao-Ting Chen, Yao-Jia Zhou, Li Tang, Yong Nie, Yi Zeng, Hui-Qi Xie, Bin Shen","doi":"10.1038/s41392-025-02136-8","DOIUrl":"https://doi.org/10.1038/s41392-025-02136-8","url":null,"abstract":"<p>Research on treating knee osteoarthritis (KOA) is becoming more challenging due to a growing number of younger patients being affected. The pathogenesis of KOA is complex for being a multifactorial disease affecting the entire joint, with remodeling of subchondral bone playing a key role in the degeneration of the overlying cartilage. Therefore, this study constructed a bipedal postmenopausal KOA mouse model to better understand how the interplay between subchondral bone remodeling and cartilage degeneration contributes to KOA development. A single-cell atlas of the osteochondral composite tissue was established. Furthermore, three novel subtypes of chondrocytes, including <i>Smoc2</i>⁺ angiogenic chondrocytes, <i>Angptl7</i>⁺ angiogenic chondrocytes, and <i>Col1a1</i>⁺ osteogenic chondrocytes, were identified in femoral condyles of KOA mice. In addition, the <i>Angptl7</i>⁺ chondrocytes promoted angiogenesis in the subchondral bone of KOA mice by interacting with endothelial cells via the FGF2-FGFR2 signaling pathway. The number of H-type vessels was increased in the subchondral bone, recruiting osteoprogenitor cells and facilitating osteogenesis in KOA mice. <i>Sparc</i>⁺ osteoblasts have negatively regulated bone mineralization and osteoblastic differentiation, aggravated the pathological remodeling of subchondral bone, and promoted the progression of KOA. The above findings have offered new targets and opened up an avenue for the therapeutic intervention of KOA.</p>","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"61 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protecting cell cycle integrity: enhanced start-codon stringency in mitosis","authors":"Omid Omrani, Kanstantsin Siniuk, Martin Fischer","doi":"10.1038/s41392-024-02123-5","DOIUrl":"https://doi.org/10.1038/s41392-024-02123-5","url":null,"abstract":"<p>A recent study published in <i>Nature</i> has uncovered a novel regulatory mechanism that enhances start-codon selection during mitosis in mammalian cells by intensifying the interaction between the 40S ribosome subunit, which binds messenger RNA (mRNA) and initiates translation, and the eukaryotic translation initiation factor 1 (eIF1), a central regulator of start-codon selection.¹ This discovery reveals a sophisticated layer of translational control that helps maintain cell viability and cell cycle stability, with potential implications for understanding cellular regulation and improving cancer therapies.</p>","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"28 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}