Apoptosis最新文献_第3页

The molecular mechanisms and therapeutic implications of PANoptosis in ischemic diseases 缺血性疾病PANoptosis的分子机制及其治疗意义。

IF 8.1 2区生物学

Apoptosis Pub Date : 2025-09-07 DOI: 10.1007/s10495-025-02157-2

Jiangpeng Wu, Xunkai Wang, Jin Peng, Jinxi Liang, Jun Lv, Lin Huang, Shenmei Wu, Chen Yao, Guiyun Jin, Tang Deng

{"title":"The molecular mechanisms and therapeutic implications of PANoptosis in ischemic diseases","authors":"Jiangpeng Wu, Xunkai Wang, Jin Peng, Jinxi Liang, Jun Lv, Lin Huang, Shenmei Wu, Chen Yao, Guiyun Jin, Tang Deng","doi":"10.1007/s10495-025-02157-2","DOIUrl":"10.1007/s10495-025-02157-2","url":null,"abstract":"<div><p>The singular forms of programmed cell death (PCD), including pyroptosis, apoptosis, and necroptosis, are inadequate for comprehensively elucidating the complex pathological mechanisms underlying ischemic diseases. PANoptosis is a unique lytic, innate immune, and inflammatory cell death pathway, initiated by innate immune sensors and driven by caspases and RIPKs through PANoptosome complexes. In diseases like cerebral ischemia, retinal ischemia, myocardial ischemia, renal ischemia, and spinal cord ischemia, targeting key regulatory factors of PANoptosis can help mitigate tissue damage. Therefore, the therapeutic potential of PANoptosis in ischemic diseases—from molecular mechanisms to clinical applications—merits further investigation. However, effectively regulating PANoptosis to achieve therapeutic outcomes remains a critical scientific challenge that must be addressed. This review focuses on the molecular mechanisms of PANoptosis in ischemic diseases and its potential therapeutic implications, aiming to provide new insights and a theoretical foundation for precision treatment in these conditions.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 9-10","pages":"2090 - 2109"},"PeriodicalIF":8.1,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10495-025-02157-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Targeting PANoptosis: a promising therapeutic strategy for ALI/ARDS. 靶向PANoptosis: ALI/ARDS的一种有前景的治疗策略。

IF 8.1 2区生物学

Apoptosis Pub Date : 2025-09-04 DOI: 10.1007/s10495-025-02168-z

Mengqi Zhang, Luorui Shang, Fangyuan Zhou, Yuju Cai, Shuhan Wang, Jinxiao Li, Yuhan Liu, Jianghua Huang, Shenglan Yang

{"title":"Targeting PANoptosis: a promising therapeutic strategy for ALI/ARDS.","authors":"Mengqi Zhang, Luorui Shang, Fangyuan Zhou, Yuju Cai, Shuhan Wang, Jinxiao Li, Yuhan Liu, Jianghua Huang, Shenglan Yang","doi":"10.1007/s10495-025-02168-z","DOIUrl":"https://doi.org/10.1007/s10495-025-02168-z","url":null,"abstract":"<p><p>Acute lung injury (ALI) is a complex, high-mortality pulmonary disease triggered by multiple etiological factors, potentially progressing to acute respiratory distress syndrome (ARDS). During the development of ALI/ARDS, a key pathological feature involves the disruption of the intact alveolar-capillary barrier, which is formed by alveolar epithelium, pulmonary interstitium, and microvascular endothelium. Under physiological conditions, cell death removes excess or dysfunctional cells, defends against pathogenic microorganisms, and thus plays a protective role while maintaining homeostasis. However, excessive clearance reactions can lead to pathological loss of pulmonary epithelial cells, endothelial cells, or macrophage-immune cells, eventually exacerbating tissue structural damage. With the discovery of various programmed cell death mechanisms, researchers have consistently uncovered the participation of cell death modes such as apoptosis, pyroptosis, necroptosis, and PANoptosis in the pathological processes underlying ALI/ARDS. Modulating these critical death pathways presents opportunities for therapeutic intervention in disease progression. Among these, PANoptosis is an independent lytic inflammatory cell death pathway initiated by innate immune sensors and driven by the PANoptosome complex, playing a core role in lung injury and infectious diseases. This review summarizes recent advancements in PANoptosis research in the context of ALI/ARDS, providing a reliable framework and direction for the targeted development of drugs acting on the PANoptosis axis to more effectively prevent and treat ALI/ARDS.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Bioactivity of mycosynthesized nanoparticles assists photothermal therapy of breast cancer cells 真菌合成纳米颗粒的生物活性有助于乳腺癌细胞的光热治疗。

IF 8.1 2区生物学

Apoptosis Pub Date : 2025-08-30 DOI: 10.1007/s10495-025-02145-6

Aya Ezzat, Marwa A. Ramadan, Jehane I. Eid, Ola S. Ahmed

{"title":"Bioactivity of mycosynthesized nanoparticles assists photothermal therapy of breast cancer cells","authors":"Aya Ezzat, Marwa A. Ramadan, Jehane I. Eid, Ola S. Ahmed","doi":"10.1007/s10495-025-02145-6","DOIUrl":"10.1007/s10495-025-02145-6","url":null,"abstract":"<div><p>Chaga mushroom (<i>Inonotus obliquus</i>) exhibits cytotoxic effects against breast cancer cells. Mycosynthesized nanoparticles, owing to their biodegradability, biocompatibility, and low toxicity, present a promising therapeutic approach. This study explored the cytotoxic potential of gold nanoparticles synthesized using Chaga mushroom extract (AuCh-NPs) combined with Light Emitting Diode (LED) irradiation (530 nm) on human breast cancer (MCF-7) cells, aiming to develop a safe and effective sensitizer for photothermal therapy. The AuCh-NPs were characterized using UV–visible spectroscopy, FTIR, TEM, particle size analysis, and zeta potential measurements. Cytotoxicity was evaluated via MTT assay under LED irradiation with total light exposure 325.8 and 488.7 J cm<sup>−2</sup>, alongside mechanistic studies involving wound healing, autophagy, cell cycle arrest, annexin V analysis, real-time PCR, and comet assays.TEM revealed spherical AuCh-NPs with sizes ranging from 15.4 to 28.9 nm. The MTT assay demonstrated enhanced cytotoxicity under LED irradiation, with AuCh-NPs exhibiting a lower IC50 (5.56 µM) than citrate-capped gold nanoparticles (AuCit-NPs, 7 µM). Cell cycle analysis revealed significant arrest in G0/G1 (91.68%) and S (7.55%) phases, while annexin V analysis confirmed apoptosis induction. Real-time PCR showed upregulation of the pro-apoptotic genes BAX, and the comet assay indicated increased double-strand DNA damage in MCF-7 cells treated with AuCh-NPs compared to AuCit-NPs. These findings highlight the superior selective cytotoxicity of AuCh-NPs against MCF7 cells, positioning them as a promising targeted agent for photothermal therapy in breast cancer treatment.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 9-10","pages":"2435 - 2454"},"PeriodicalIF":8.1,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10495-025-02145-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Dual-functional Anti-hPSMAEC domain nanocapsules for targeted inhibition of prostate tumor growth 双功能抗hpsmaec结构域纳米胶囊靶向抑制前列腺肿瘤生长

IF 8.1 2区生物学

Apoptosis Pub Date : 2025-08-21 DOI: 10.1007/s10495-025-02163-4

Heng Yang, Jian He, Yujun Chen, Xiaochen Zhou, Xiaofeng Cheng, Zhenhao Zeng, Min Zhou, Gongxian Wang

{"title":"Dual-functional Anti-hPSMAEC domain nanocapsules for targeted inhibition of prostate tumor growth","authors":"Heng Yang, Jian He, Yujun Chen, Xiaochen Zhou, Xiaofeng Cheng, Zhenhao Zeng, Min Zhou, Gongxian Wang","doi":"10.1007/s10495-025-02163-4","DOIUrl":"10.1007/s10495-025-02163-4","url":null,"abstract":"<div><p>Addressing prostate cancer, particularly in its aggressive forms, poses challenges that call for innovative treatment modalities. Our research focuses on developing a nanotechnological solution to enhance targeted cancer therapy. We have synthesized advanced nanocapsules embedded with indocyanine green (ICG) and conjugated with the Anti-hPSMA<sup>EC domain</sup> to improve specificity towards prostate cancer cells. These nanocapsules are engineered to perform dual-mode phototherapy through photothermal and photodynamic mechanisms. In vitro experiments demonstrated the nanocapsules effectively target and induce apoptosis in prostate cancer cells upon exposure to near-infrared light. Furthermore, in vivo assessments in murine models revealed excellent tumor localization and a substantial reduction in tumor volume with minimal impact on healthy tissues. This innovative approach underscores the potential of nanotechnology to transform the therapeutic landscape of prostate cancer by achieving precise targeting and reducing systemic side effects. Such nanocapsule systems’ continued development and refinement may substantially improve clinical outcomes and provide promising therapeutic strategies for treating complex cancers.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div><p>APCI nanoparticles for sensitive tumor imaging andenhanced PTT & in vivo PDT. (A) Schematic design of APCI for targeted cancer cell delivery; (B) visualization and therapy of orthotopic and metastatic prostate cancer.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 9-10","pages":"2401 - 2420"},"PeriodicalIF":8.1,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

The role of epigenetic regulation in cuproptosis, ferroptosis and NETosis in the pathogenesis of autoimmune diseases. 铜下垂、铁下垂和NETosis在自身免疫性疾病发病机制中的表观遗传调控作用。

IF 8.1 2区生物学

Apoptosis Pub Date : 2025-08-21 DOI: 10.1007/s10495-025-02158-1

Wenshan Zhao, Leping Wang, Hanru Jia, Jiali Shan, Yi Zhang, Hejia Gu, Yongchao Xu, Xinke Ma, Peiying Li, Jing Wu

{"title":"The role of epigenetic regulation in cuproptosis, ferroptosis and NETosis in the pathogenesis of autoimmune diseases.","authors":"Wenshan Zhao, Leping Wang, Hanru Jia, Jiali Shan, Yi Zhang, Hejia Gu, Yongchao Xu, Xinke Ma, Peiying Li, Jing Wu","doi":"10.1007/s10495-025-02158-1","DOIUrl":"https://doi.org/10.1007/s10495-025-02158-1","url":null,"abstract":"<p><p>Ferroptosis, cuproptosis and NETosis are various important forms of non-apoptotic programmed cell death, with research involving these subtypes of cell death exponentially increased in recent years. Ferroptosis is a unique iron-dependent form of cell death that involves iron transport as well as redox homeostasis within the cell. Cuproposis is a new phenomenon of cell death, primarily driven by the excessive intracellular accumulation of copper ions, with its occurrence and development closely associated with mitochondrial dysfunction. NETosis on the other hand occurs due to the release of neutrophil extracellular traps by neutrophils upon their stimulation. Currently, various of types of autoimmune diseases (AD) have been clinically identified, with their etiology established to be multifactorial. In this review, we specifically investigate the correlation between these three non-apoptotic programmed cell deaths and the pathogenesis of AD, as well as elucidate the internal mechanisms involving miRNA, DNA methylation, histone modifications, related transcription factors, and non-coding RNAs from an epigenetic perspective. Additionally, we analyzed the molecular and pathophysiological mechanisms of ferroptosis, cupropopsis, and NETosis in the development of AD. By examining the therapeutic potential of emerging immune checkpoint targets, this review aims to offer novel insights and strategies to address the ongoing challenges in the prevention and treatment of autoimmune diseases.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

The intersection of mitochondria, lipids, and ferroptosis: a new avenue for dry age-related macular degeneration. 线粒体，脂质和铁下垂的交叉点：干性年龄相关性黄斑变性的新途径。

IF 8.1 2区生物学

Apoptosis Pub Date : 2025-08-21 DOI: 10.1007/s10495-025-02165-2

Jacob Dohl, Gordon Burns, Mithalesh Singh

引用次数: 0

Integrative analysis of RiboSis-related gene expression in colorectal cancer: implications for prognosis and immunotherapy. 结直肠癌中核糖核酸相关基因表达的综合分析：对预后和免疫治疗的影响。

IF 8.1 2区生物学

Apoptosis Pub Date : 2025-08-21 DOI: 10.1007/s10495-025-02166-1

Wei Song, Min Zhou, Yatao Wang, Fengqin Guo, Yanliang Liu

{"title":"Integrative analysis of RiboSis-related gene expression in colorectal cancer: implications for prognosis and immunotherapy.","authors":"Wei Song, Min Zhou, Yatao Wang, Fengqin Guo, Yanliang Liu","doi":"10.1007/s10495-025-02166-1","DOIUrl":"https://doi.org/10.1007/s10495-025-02166-1","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a prevalent and lethal malignancy that imposes significant burdens on patients and healthcare systems worldwide. This study aimed to explore the significance of ribosome biogenesis (RiboSis)-related genes (RRGs) in CRC and their clinical implications. The scRNA-seq data of three CRC tissues were sourced from the Gene Expression Omnibus (GEO) database. Nonnegative matrix factorization (NMF) was employed to categorize cell subtypes associated with RiboSis. An integrative machine learning approach encompassing ten algorithms was subsequently implemented to develop a prognostic signature. Our research revealed 295 differentially expressed RiboSis-related genes (DERRGs) associated with survival outcomes, with a notable RiboSis score that was markedly higher in CRC tissues than in normal counterparts. Univariate Cox analysis revealed 25 DERRGs with significant survival differences (P < 0.05). scRNA-seq of 26,961 cells from 13 CRC samples revealed eight major cell types, with T and B cells predominantly enriched in immune response pathways. InferCNV analysis distinguished malignant epithelial cells on the basis of copy number variations, and NMF identified four RiboSis-related cell subtypes. Our RiboSis-related prognostic model, validated across the TCGA, GSE17536, and GSE39582 datasets, demonstrated high predictive accuracy. Notably, low RiboSis signature scores were correlated with reduced immune evasion risk and upregulated immune checkpoint genes, suggesting enhanced responsiveness to immunotherapy. Among the 8 model genes, PFDN2 was considered the hub gene. The experimental results of PFDN2 in this RiboSis signature indicated that PFDN2 expression is elevated in CRC tissues and that PFDN2 knockdown promotes the proliferation, migration, and invasion of CRC cells. This study underscores the potential of RRGs as biomarkers and therapeutic targets, offering new avenues for personalized CRC management.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Comprehensive analysis of regulated cell death pathways: intrinsic disorder, protein–protein interactions, and cross-pathway communication 调控细胞死亡途径的综合分析：内在紊乱、蛋白-蛋白相互作用和交叉通路通讯。

IF 8.1 2区生物学

Apoptosis Pub Date : 2025-08-19 DOI: 10.1007/s10495-025-02161-6

Oleksandr Sorokin, Frank Hause, Alice Wedler, Tala Alakhras, Theresa Bauchspiess, Anne Dietrich, Wiebke F. Günther, Coninika Guha, Kingsley B. Obika, Joshua Kraft, Ezgi Mehteroglu, Jan Oehlschläger, Erik Siefke, Mark Tawfeik, Toni K. Träger, Florian W. Otto, Manuel Weber, Felix Wiebe, Andrea Sinz, Vladimir N. Uversky

{"title":"Comprehensive analysis of regulated cell death pathways: intrinsic disorder, protein–protein interactions, and cross-pathway communication","authors":"Oleksandr Sorokin, Frank Hause, Alice Wedler, Tala Alakhras, Theresa Bauchspiess, Anne Dietrich, Wiebke F. Günther, Coninika Guha, Kingsley B. Obika, Joshua Kraft, Ezgi Mehteroglu, Jan Oehlschläger, Erik Siefke, Mark Tawfeik, Toni K. Träger, Florian W. Otto, Manuel Weber, Felix Wiebe, Andrea Sinz, Vladimir N. Uversky","doi":"10.1007/s10495-025-02161-6","DOIUrl":"10.1007/s10495-025-02161-6","url":null,"abstract":"<div><p>Regulated cell death (RCD) pathways—once viewed as linear, independent processes—are now recognized as components of a dynamic, interconnected molecular network that dictates cellular fate in health and disease. This study presents a systematic meta-analysis of thirteen major RCD pathways, examining their molecular mechanisms, triggers, and interconnections through protein–protein interaction (PPI) networks. Using custom bioinformatics approaches, we unveiled the interactome of proteins involved in apoptosis, autophagy-dependent cell death, cellular senescence, mitotic catastrophe, entotic cell death, ferroptosis, cuproptosis, immunogenic cell death, lysosome-dependent cell death, mitochondrial permeability transition-driven necrosis, necroptosis, neutrophil extracellular trap formation-related cell death (NETosis), parthanatos, and pyroptosis. By integrating data from an extensive literature review with STRING database analyses, we identified previously unrecognized cross-pathway interactions and regulatory nodes where special attention was given to the role of intrinsically disordered proteins (IDPs) in these pathways. Our findings reveal a complex interplay between different RCD mechanisms and highlight potential therapeutic targets for diseases characterized by dysregulated cell death programs, including cancer and autoimmune disorders. This comprehensive analysis provides new insights into the molecular architecture of RCD pathways and their cooperative functions in maintaining cellular homeostasis.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 9-10","pages":"2110 - 2162"},"PeriodicalIF":8.1,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Do fungi also undergo "ferroptosis"? A microscopic exploration of cellular death. 真菌也会发生“铁下垂”吗？细胞死亡的显微探索。

IF 8.1 2区生物学

Apoptosis Pub Date : 2025-08-19 DOI: 10.1007/s10495-025-02164-3

Xingxing Shang, Qian Zhang, Qingli Yang, Fangyuan Zhao, Jian Ju

{"title":"Do fungi also undergo \"ferroptosis\"? A microscopic exploration of cellular death.","authors":"Xingxing Shang, Qian Zhang, Qingli Yang, Fangyuan Zhao, Jian Ju","doi":"10.1007/s10495-025-02164-3","DOIUrl":"10.1007/s10495-025-02164-3","url":null,"abstract":"<p><p>Ferroptosis, a recently identified form of programmed cell death, has shown promising advancements in mammalian cell studies. However, research on ferroptosis in fungi is still in its nascent stages, resulting in limited understanding of its regulatory mechanisms. Given the unique regulatory mechanisms of ferroptosis and its significant implications for fungal research, this review focuses on the regulatory mechanisms of fungal ferroptosis, highlighting key target proteins and potential intervention strategies. Furthermore, the interplay between fungal ferroptosis and organelles is examined, analyzing the molecular logic of organelle-mediated ferroptosis, including their core functions and mechanisms promoting or inhibiting ferroptosis. Based on these findings, potential antifungal agents targeting the fungal ferroptosis pathway are summarized, along with their primary target pathways, key target proteins, and mechanisms of action. We also discuss the main characteristics of fungal ferroptosis and provide perspectives on future research directions. This review aims to provide new insights into the in-depth study of fungal ferroptosis and the development and design of novel antifungal agents targeting fungal ferroptosis. For instance, targeting key proteins or signaling pathways related to fungal ferroptosis may lead to the design of more effective antifungal drugs, overcoming the drug resistance issues of various drug-resistant fungi in current clinical settings.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

FOXP2/SOS1/AKT negative feedback loop inhibits cell proliferation in KRAS-mutant colorectal cancer FOXP2/SOS1/AKT负反馈环抑制kras突变型结直肠癌细胞增殖

IF 8.1 2区生物学

Apoptosis Pub Date : 2025-08-14 DOI: 10.1007/s10495-025-02154-5

Jinpu Liu, Yayun Wang, Yuya Liu, Hanwei Mei, Qiaonan Zhang, Zhanhua Gao, Miao Zhang, Zhen Yang, Huaqing Wang, Minghan Qiu

{"title":"FOXP2/SOS1/AKT negative feedback loop inhibits cell proliferation in KRAS-mutant colorectal cancer","authors":"Jinpu Liu, Yayun Wang, Yuya Liu, Hanwei Mei, Qiaonan Zhang, Zhanhua Gao, Miao Zhang, Zhen Yang, Huaqing Wang, Minghan Qiu","doi":"10.1007/s10495-025-02154-5","DOIUrl":"10.1007/s10495-025-02154-5","url":null,"abstract":"<div><p>FOXP2, a member of the Forkhead box transcription factor family, has been implicated in diverse biological processes and malignancies. However, its role in colorectal cancer (CRC), particularly in the context of KRAS mutations, remains poorly defined. Here, we analyzed FOXP2 expression in CRC datasets and clinical specimens, and conducted functional assays—including colony formation, cell viability, EdU incorporation, and cell cycle analysis—in KRAS-mutant CRC cell lines with FOXP2 overexpression or knockdown. Western blotting, dual-luciferase reporter assays, and in vivo xenograft models were used to explore the underlying mechanisms. FOXP2 was significantly downregulated in CRC tissues and its high expression correlated with favorable prognosis in KRAS-mutant patients. Functionally, FOXP2 overexpression suppressed cell proliferation, induced G0/G1-phase arrest, and inhibited PI3K/AKT signaling. Mechanistically, FOXP2 transcriptionally repressed SOS1, thereby attenuating downstream AKT activation. Notably, AKT activation enhanced FOXP2 expression, indicating a FOXP2/SOS1/AKT negative feedback loop. Collectively, our findings suggest that FOXP2 inhibits proliferation in KRAS-mutant CRC by suppressing SOS1-mediated PI3K/AKT signaling, and may serve as a prognostic biomarker and potential therapeutic target in KRAS-driven CRC.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 9-10","pages":"2455 - 2465"},"PeriodicalIF":8.1,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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