Signal Transduction and Targeted Therapy最新文献

{"title":"Melatonin synergizes with prostaglandin E2 to enhance YAP-mediated regenerative epithelial cell emergence during intestinal repair.","authors":"Yoojin Seo,Ji-Su Ahn,Hansong Lee,Yun Hak Kim,Hyung-Sik Kim","doi":"10.1038/s41392-025-02248-1","DOIUrl":"https://doi.org/10.1038/s41392-025-02248-1","url":null,"abstract":"","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"38 1","pages":"163"},"PeriodicalIF":39.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087720","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":"Large vesicles from ageing neutrophils: novel safeguards for the resolution of inflammation.","authors":"Christopher Dietz-Fricke,Florian R Greten","doi":"10.1038/s41392-025-02244-5","DOIUrl":"https://doi.org/10.1038/s41392-025-02244-5","url":null,"abstract":"","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"2 1","pages":"162"},"PeriodicalIF":39.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087719","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":"Vascular endothelial growth factor signaling in health and disease: from molecular mechanisms to therapeutic perspectives.","authors":"Chunsik Lee,Myung-Jin Kim,Anil Kumar,Han-Woong Lee,Yunlong Yang,Yonghwan Kim","doi":"10.1038/s41392-025-02249-0","DOIUrl":"https://doi.org/10.1038/s41392-025-02249-0","url":null,"abstract":"Vascular endothelial growth factor (VEGF) signaling is a critical regulator of vasculogenesis, angiogenesis, and lymphangiogenesis, processes that are vital for the development of vascular and lymphatic systems, tissue repair, and the maintenance of homeostasis. VEGF ligands and their receptors orchestrate endothelial cell proliferation, migration, and survival, playing a pivotal role in dynamic vascular remodeling. Dysregulated VEGF signaling drives diverse pathological conditions, including tumor angiogenesis, cardiovascular diseases, and ocular disorders. Excessive VEGF activity promotes tumor growth, invasion, and metastasis, while insufficient signaling contributes to impaired wound healing and ischemic diseases. VEGF-targeted therapies, such as monoclonal antibodies and tyrosine kinase inhibitors, have revolutionized the treatment of diseases involving pathological angiogenesis, offering significant clinical benefits in oncology and ophthalmology. These therapies inhibit angiogenesis and slow disease progression, but they often face challenges such as therapeutic resistance, suboptimal efficacy, and adverse effects. To further explore these issues, this review provides a comprehensive overview of VEGF ligands and receptors, elucidating their molecular mechanisms and regulatory networks. It evaluates the latest progress in VEGF-targeted therapies and examines strategies to address current challenges, such as resistance mechanisms. Moreover, the discussion includes emerging therapeutic strategies such as innovative drug delivery systems and combination therapies, highlighting the continuous efforts to improve the effectiveness and safety of VEGF-targeted treatments. This review highlights the translational potential of recent discoveries in VEGF biology for improving patient outcomes.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"8 1","pages":"170"},"PeriodicalIF":39.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087718","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":"Deep mining in the dorsal raphe: cholecystokinin-expressing neurons encode satiation-related cues to regulate meal size.","authors":"Niels Röhrdanz,Peer Wulff,Kira Balueva","doi":"10.1038/s41392-025-02240-9","DOIUrl":"https://doi.org/10.1038/s41392-025-02240-9","url":null,"abstract":"","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"121 1","pages":"155"},"PeriodicalIF":39.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065749","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":"Platelets and diseases: signal transduction and advances in targeted therapy.","authors":"Yuchen Tian,Yao Zong,Yidan Pang,Zhikai Zheng,Yiyang Ma,Changqing Zhang,Junjie Gao","doi":"10.1038/s41392-025-02198-8","DOIUrl":"https://doi.org/10.1038/s41392-025-02198-8","url":null,"abstract":"Platelets are essential anucleate blood cells that play pivotal roles in hemostasis, tissue repair, and immune modulation. Originating from megakaryocytes in the bone marrow, platelets are small in size but possess a highly specialized structure that enables them to execute a wide range of physiological functions. The platelet cytoplasm is enriched with functional proteins, organelles, and granules that facilitate their activation and participation in tissue repair processes. Platelet membranes are densely populated with a variety of receptors, which, upon activation, initiate complex intracellular signaling cascades. These signaling pathways govern platelet activation, aggregation, and the release of bioactive molecules, including growth factors, cytokines, and chemokines. Through these mechanisms, platelets are integral to critical physiological processes such as thrombosis, wound healing, and immune surveillance. However, dysregulated platelet function can contribute to pathological conditions, including cancer metastasis, atherosclerosis, and chronic inflammation. Due to their central involvement in both normal physiology and disease, platelets have become prominent targets for therapeutic intervention. Current treatments primarily aim to modulate platelet signaling to prevent thrombosis in cardiovascular diseases or to reduce excessive platelet aggregation in other pathological conditions. Antiplatelet therapies are widely employed in clinical practice to mitigate clot formation in high-risk patients. As platelet biology continues to evolve, emerging therapeutic strategies focus on refining platelet modulation to enhance clinical outcomes and prevent complications associated with platelet dysfunction. This review explores the structure, signaling pathways, biological functions, and therapeutic potential of platelets, highlighting their roles in both physiological and pathological contexts.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"18 1","pages":"159"},"PeriodicalIF":39.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065835","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":"Anti-BCL2 therapy eliminates giant congenital melanocytic nevus by senolytic and immune induction.","authors":"Boxuan Wei,Qingxiong Yu,Jiamin Jin,Danli Zhu,Bohan Lai,Jieyu Gu,Ran Yang,Huailiang Huang,Hongzhan Lin,Liang Zhang,Tao Zan,Feng Xie,Kang Zhang,Qingfeng Li","doi":"10.1038/s41392-025-02247-2","DOIUrl":"https://doi.org/10.1038/s41392-025-02247-2","url":null,"abstract":"Giant congenital melanocytic nevus (GCMN) is a RAS/RAF mutation-driven syndrome characterized by extensive melanocytic lesions, posing psychological challenges and a lifelong risk of malignancy. Existing treatments like surgical resection and laser therapy fail to fully remove lesions, and MAPK inhibitors show limited efficacy. This study identified a predominant population of senescent cells and a minority of proliferative cells in GCMN, necessitating dual-targeted strategies. We found that the anti-apoptotic protein BCL2 is expressed in both senescent and proliferative cells from GCMN patients with various gene mutations. Coexpression of P16 and BCL2 indicated a phenotype of growth arrest and cell survival. BCL2 inhibitors (BCL2i) showed significant cytotoxicity to GCMN cells in vitro. Hypopigmentation and GCMN cell clearance were observed in patient-derived xenograft models and in NrasQ61K-mutated and BrafV600E-mutated transgenic models following BCL2i treatment. Histology of regressed GCMN indicated extensive immune cell infiltration, suggesting immune involvement. Single-cell sequencing and immunostaining revealed that activated neutrophils formed extracellular traps, synergizing with BCL2i to treat GCMN. Neutrophil depletion and immunosuppression reduce treatment efficacy, highlighting the crucial role of the immune response post-BCL2i treatment. Long-term follow-up showed no recurrence, with neutrophils and T cells residing in the dermis, indicating memory immune reactions. These findings present a promising therapeutic strategy and underscore the translational potential of BCL2i in treating GCMN.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"28 1","pages":"161"},"PeriodicalIF":39.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065750","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":"Quantum biological convergence: quantum computing accelerates KRAS inhibitor design.","authors":"Taeho Kwon,Hakjin Kim","doi":"10.1038/s41392-025-02239-2","DOIUrl":"https://doi.org/10.1038/s41392-025-02239-2","url":null,"abstract":"","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"139 1 1","pages":"152"},"PeriodicalIF":39.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945354","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":"Exosomal transfer of pro-pyroptotic miR-216a-5p exacerbates anthracycline cardiotoxicity through breast cancer-heart pathological crosstalk.","authors":"Yan Ma,Yongjun Wang,Renzheng Chen,Yabin Wang,Yan Fang,Cheng Qin,Tianhu Wang,Xiaoying Shen,Tingwen Zhou,Lei Tian,Ting Sun,Li Fan,Xiaoning Wang,Dong Han,Feng Cao","doi":"10.1038/s41392-025-02245-4","DOIUrl":"https://doi.org/10.1038/s41392-025-02245-4","url":null,"abstract":"Doxorubicin (DOX) is the most effective chemotherapeutic for breast cancer, but it is usually associated with severe cardiotoxicity. Further investigation to alleviate its side effects is essential. The present study investigated the mechanism of the cross-organ communication between tumors and the heart and potential intervention targets. Morphological bubble-like protrusions were observed in both adult murine ventricular cardiomyocytes (AMVCs) and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) cocultured with breast cancer cells (BCCs), along with elevated expression of pyroptosis-related proteins. Exosomes (EXOs) from DOX-treated BCCs aggravated DOX-induced cardiotoxicity (DOXIC) in an orthotopic mouse model of breast cancer. Blocking miRNAs by knocking down Rab27a or inhibiting the release of EXOs in cancer tissue by Dicer enzyme knockout attenuated this additional injury effect. Exosomal miRNA sequencing revealed that miR-216a-5p is especially upregulated in EXOs from DOX-induced BCCs. Mechanistically, miR-216a-5p was upregulated by enhanced transcription mediated by DOX-induced AMP-dependent transcription factor 3 (ATF3) and packaged into EXOs by splicing factor 3b subunit 4 (SF3B4) in BCCs. Itchy E3 ubiquitin-protein ligase (ITCH) was identified as a novel downstream target mRNA of miR-216a-5p. ITCH negatively mediated thioredoxin-interacting protein (TXNIP) ubiquitination to activate the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome pathway, ultimately leading to cardiomyocyte pyroptosis. Our findings revealed novel cross-organ pathogenic communication between breast cancer and the heart through the exosomal miR-216a-5p-mediated ITCH/TXNIP/NLRP3 pathway, which drives cardiomyocyte pyroptosis. These findings suggest that targeting myocardial miR-216a-5p or blocking harmful EXOs from breast cancer is a potential therapeutic strategy for alleviating DOXIC.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"32 1","pages":"157"},"PeriodicalIF":39.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945378","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":"Loss of the aryl hydrocarbon receptor promotes cancer cell resistance to BRAFV600E targeted therapies.","authors":"Mourad Zerfaoui,Dharmeshkumar Patel,Yueqi Zhang,Raymond F Schinazi,Youssef Errami","doi":"10.1038/s41392-025-02235-6","DOIUrl":"https://doi.org/10.1038/s41392-025-02235-6","url":null,"abstract":"","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"3 1","pages":"158"},"PeriodicalIF":39.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945240","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":"Enhancing the anti-aging potential of the nigrostriatal dopamine system to counteract age-related motor decline.","authors":"Youngpyo Nam,Sehwan Kim,Jun-Yeong Lee,Jaekwang Kim,Sang Ryong Kim","doi":"10.1038/s41392-025-02234-7","DOIUrl":"https://doi.org/10.1038/s41392-025-02234-7","url":null,"abstract":"","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"230 1","pages":"153"},"PeriodicalIF":39.3,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932767","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}