Cancer letters最新文献_第7页

Aberrant PLAC8 expression characterizes glioblastoma with temozolomide resistance and an immunosuppressive microenvironment 具有替莫唑胺耐药和免疫抑制微环境的胶质母细胞瘤的异常PLAC8表达

IF 9.1 1区医学

Cancer letters Pub Date : 2025-05-19 DOI: 10.1016/j.canlet.2025.217805

Han She , Tian-Ran Li , Guozhi Zhao , Liang Yi , Qing Liu , Zheng-Chao Liu , Hao-Yu Pei , Xunjia Li , Deyu Zuo , Qingxiang Mao , Yong Li

{"title":"Aberrant PLAC8 expression characterizes glioblastoma with temozolomide resistance and an immunosuppressive microenvironment","authors":"Han She , Tian-Ran Li , Guozhi Zhao , Liang Yi , Qing Liu , Zheng-Chao Liu , Hao-Yu Pei , Xunjia Li , Deyu Zuo , Qingxiang Mao , Yong Li","doi":"10.1016/j.canlet.2025.217805","DOIUrl":"10.1016/j.canlet.2025.217805","url":null,"abstract":"<div><div>Glioblastoma (GBM), Isocitrate Dehydrogenase-wildtype (IDH-WT) represents the most prevalent and clinically aggressive subtype of adult diffuse gliomas, typically associated with poor prognosis. Temozolomide (TMZ) remains the first-line chemotherapeutic agent for GBM; however, the emergence of TMZ resistance represents a major therapeutic obstacle in clinical practice. This study identifies placenta-specific 8 (PLAC8) as a novel mediator of TMZ resistance in IDH-WT GBM. Elevated PLAC8 expression was strongly correlated with poorer survival rates, higher tumor grades in glioma, establishing it as an independent prognostic factor. Notably, consistent upregulation of PLAC8 was observed in both TMZ-resistant GBM cells and TMZ-treated patients, suggesting its potential as a biomarker for TMZ resistance. Mechanistic studies revealed that PLAC8 regulates TMZ sensitivity in GBM cells through the AKT-mTOR signaling pathway. Additionally, integrated bioinformatics and clinical analyses demonstrated that PLAC8 expression positively correlates with immune cell infiltration while promoting an immunosuppressive tumor microenvironment and modulating immunotherapy-related biomarkers, suggesting its potential as a predictive biomarker for immunotherapy response. In conclusion, PLAC8 represents a promising biomarker and therapeutic target for overcoming TMZ resistance and guiding immunotherapy in GBM. This study provides valuable insights for the development of personalized treatment strategies aimed at improving patient outcomes.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"625 ","pages":"Article 217805"},"PeriodicalIF":9.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144107463","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}

引用次数: 0

SMARCA4: Promises and challenges in the treatment of cancers SMARCA4：癌症治疗的希望和挑战

IF 9.1 1区医学

Cancer letters Pub Date : 2025-05-19 DOI: 10.1016/j.canlet.2025.217811

Wei Ye , Ding An , Wen-Bin Ou

{"title":"SMARCA4: Promises and challenges in the treatment of cancers","authors":"Wei Ye , Ding An , Wen-Bin Ou","doi":"10.1016/j.canlet.2025.217811","DOIUrl":"10.1016/j.canlet.2025.217811","url":null,"abstract":"<div><div>The SWI/SNF (switch/sucrose non-fermentable) related BAF (BRG1/BRM-related factor) chromatin remodeling complex subunit ATPase 4 (<em>SMARCA4</em>) is a gene with a high mutation frequency in the SWI/SNF complex. It plays a role as an ATP-dependent catalytic subunit, participates in remodeling chromatin structure and regulation of gene expression, and is closely related to the poor prognosis of malignant tumors. It is imperative to conduct a comprehensive investigation into the distinctive biological functions and mechanisms by which SMARCA4 contributes to cancer development and to devise targeted therapeutic strategies. Despite numerous studies associating SMARCA4 with the regulation of essential genes, ferroptosis, autophagy, lipid metabolism, and oxidative stress, the precise mechanisms of SMARCA4 in tumors remain unclear. Patients with <em>SMARCA4</em> mutations exhibit a poor prognosis and demonstrate limited responsiveness to surgery, targeted therapies, immunotherapy, and chemotherapies. Thus, SMARCA4 emerges as a promising biomarker and therapeutic target. However, the development of more effective precision therapy tools remains an urgent unmet need. The unique molecular characteristics of SMARCA4 pose significant challenges for targeted drug development. Notably, the discovery of inhibitors targeting SMARCA4 synthetic lethal partners and associated pathways has marked a breakthrough in this field. Monotherapies directed against SMARCA4 face several limitations, including drug resistance, suboptimal objective response rates, and dose-limiting toxicities. Consequently, the exploration of combinatorial therapeutic strategies for SMARCA4 deficiency populations represents a critical direction for future clinical translation.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"625 ","pages":"Article 217811"},"PeriodicalIF":9.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144107462","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}

引用次数: 0

Ketogenesis instigates immune suppression in enzalutamide resistant prostate cancer via OTUD7B β-hydroxybutyrylation 生酮通过OTUD7B β-羟基丁基化激活恩杂鲁胺耐药前列腺癌的免疫抑制。

IF 9.1 1区医学

Cancer letters Pub Date : 2025-05-18 DOI: 10.1016/j.canlet.2025.217808

Haoran Jiang , Yuan Zeng , Weiqiang Ning , Junkai Hong , Moyang Zhu , Ping Li , Fangdie Ye , Zhifa Chen , Haoran Chen , Wei Chen , Gang Li , Hang Huang

{"title":"Ketogenesis instigates immune suppression in enzalutamide resistant prostate cancer via OTUD7B β-hydroxybutyrylation","authors":"Haoran Jiang , Yuan Zeng , Weiqiang Ning , Junkai Hong , Moyang Zhu , Ping Li , Fangdie Ye , Zhifa Chen , Haoran Chen , Wei Chen , Gang Li , Hang Huang","doi":"10.1016/j.canlet.2025.217808","DOIUrl":"10.1016/j.canlet.2025.217808","url":null,"abstract":"<div><div>Next-generation androgen receptor inhibitors are the primary treatment for metastatic prostate cancer. Unfortunately, the majority of patients rapidly develop resistance. Resistance to enzalutamide has been linked to the emergence of an immunosuppressive tumor, although the underlying mechanisms remain poorly understood. In this study, we observed a marked overexpression of enzymes involved in the ketogenic pathway in enzalutamide-induced castration-resistant prostate cancer, which contributed to immune desertification and resistance to immunotherapy. Mechanistically, upregulation of the ketogenic pathway led to the accumulation of β-hydroxybutyrate, which promoted β-hydroxybutyrylation of the cell cycle-regulated deubiquitinase OTUD7B at lysine 511. This modification impaired the degradation of APC/C substrates, resulting in a subsequent reduction in cytoplasmic double-stranded DNA accumulation, thereby attenuating cGAS-STING activation and interferon expression. These findings shed light on the metabolic adaptations and immune escape driven by androgen receptor signaling inhibitors, potentially informing the development of more effective and durable therapeutic approaches in the near future.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"625 ","pages":"Article 217808"},"PeriodicalIF":9.1,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109736","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}

引用次数: 0

Preferential release of microRNAs via extracellular vesicles is associated with ductal carcinoma in situ to invasive breast cancer progression 微rna通过细胞外囊泡优先释放与导管原位癌浸润性乳腺癌进展相关

IF 9.1 1区医学

Cancer letters Pub Date : 2025-05-17 DOI: 10.1016/j.canlet.2025.217794

Sugantha Priya Elayapillai , Samrita Dogra , Cole Hladik , James Lausen , Matthew Bruns , Amy Gin Gossett , Fariba Behbod , Chao Xu , Roy Zhang , Wei-Qun Ding , Bethany N. Hannafon

{"title":"Preferential release of microRNAs via extracellular vesicles is associated with ductal carcinoma in situ to invasive breast cancer progression","authors":"Sugantha Priya Elayapillai , Samrita Dogra , Cole Hladik , James Lausen , Matthew Bruns , Amy Gin Gossett , Fariba Behbod , Chao Xu , Roy Zhang , Wei-Qun Ding , Bethany N. Hannafon","doi":"10.1016/j.canlet.2025.217794","DOIUrl":"10.1016/j.canlet.2025.217794","url":null,"abstract":"<div><div>Ductal carcinoma in situ (DCIS) is a precancerous condition that increases the risk of invasive breast cancer (IBC), but not all DCIS cases progress to IBC. The molecular factors driving this transition remain unclear. Small extracellular vesicles (sEVs), or exosomes, play a role in advanced cancer progression, though their function in DCIS is poorly understood. This study explores the role of sEVs and their RNA content in DCIS progression. We found that Rab27A, a key regulator of exosome release, is upregulated in DCIS and IBC tissues compared to normal breast tissue. Inhibiting sEV release by knocking down Rab27A disrupted pro-invasive signaling and reduced invasion in a DCIS mouse model. Using the MCF10 breast cancer progression series, we observed increased microRNA (miRNA) content in sEVs as cells transitioned from normal to malignant, with the most significant differential miRNA expression seen in IBC-derived sEVs. In vivo, DCIS progression raised circulating sEV miRNA levels, which were reduced by Rab27A knockdown. Reintroducing miR-205, enriched in IBC-derived sEVs, suppressed DCIS cell proliferation, invasion, and epithelial-mesenchymal transition (EMT) markers. Co-expression of miR-205 with Rab27A knockdown also suppressed TGF-β signaling, activated MAPK p38, and induced cell cycle arrest and apoptosis. These findings show that the RNA cargo of sEVs changes during malignancy, with specific miRNAs driving DCIS progression. Re-expression of miR-205 offers a promising therapeutic approach to prevent DCIS from becoming invasive.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"625 ","pages":"Article 217794"},"PeriodicalIF":9.1,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101418","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}

引用次数: 0

Corrigendum to “PA28γ acts as a dual regulator of IL-6 and CCL2 and contributes to tumor angiogenesis in oral squamous cell carcinoma” [Cancer Lett. 428 (2018) 192–200] “PA28γ作为IL-6和CCL2的双重调节因子，有助于口腔鳞状细胞癌的肿瘤血管生成”的更正[癌症杂志]. 428 (2018)192-200]

IF 9.1 1区医学

Cancer letters Pub Date : 2025-05-17 DOI: 10.1016/j.canlet.2025.217787

Sai Liu , Dongjuan Liu , Xin Zeng , Jiongke Wang , Jiajia Liu , Junxin Cheng , Kexin Lei , Hetian Bai , Ning Ji , Min Zhou , Lu Jiang , Hongxia Dan , Jing Li , Qianming Chen

引用次数: 0

Microbial interactions induce the mutational signature of mismatch repair deficiency in colorectal cancer and associated with EPPK1 mutations 微生物相互作用诱导结直肠癌错配修复缺陷的突变特征并与EPPK1突变相关

IF 9.1 1区医学

Cancer letters Pub Date : 2025-05-16 DOI: 10.1016/j.canlet.2025.217807

Dandan Hu , Jialin Zhao , Miaoqing Wu , Ying Zhou , Beile Lyu , Chaoqun Xu , Chao Huang , Zixuan Su , Hui Zhang , Jintao Guo , Weiwei Tang , Gong Chen , Qiyuan Li

{"title":"Microbial interactions induce the mutational signature of mismatch repair deficiency in colorectal cancer and associated with EPPK1 mutations","authors":"Dandan Hu , Jialin Zhao , Miaoqing Wu , Ying Zhou , Beile Lyu , Chaoqun Xu , Chao Huang , Zixuan Su , Hui Zhang , Jintao Guo , Weiwei Tang , Gong Chen , Qiyuan Li","doi":"10.1016/j.canlet.2025.217807","DOIUrl":"10.1016/j.canlet.2025.217807","url":null,"abstract":"<div><div>To better understand the impact of microbial interactions on the clonal evolution of colorectal cancer (CRC), we conducted high-resolution profiling of the gut microbiome of 101 treatment-naïve primary CRC patients using nanopore sequencing. We performed an integrated analysis of microbiome and tumor exome data to identify symbiotic microbes that interactively influence the mutational processes and the subsequent clonality of CRC. Our results suggested that <em>Dialister pneumosintes</em> and <em>Fusobacterium animalis</em> were both associated with somatic <em>EPPK1</em> mutations and promote <strong>SBS6</strong> (mismatch repair deficiency, dMMR) activity. Notably, we showed that the symbiotic architecture of <em>Dialister pneumosintes</em> and <em>Fusobacterium animalis</em> undergoes significant changes with the mutational status of <em>EPPK1</em>. In addition, we identified specific metabolic pathways involving key metabolites that potentially mediate microbial interactions in CRC. These findings provide new insights into the interplay between the gut microbiome and the mutation landscape of colorectal cancer, thereby informing the clonal evolution of CRC and new strategies for precision medicine.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"625 ","pages":"Article 217807"},"PeriodicalIF":9.1,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092863","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}

引用次数: 0

Lactylation-boosted polycomb repression of KLF4 elicits glycolysis in retinoblastoma: A positive feedback circuit between histone modifications 乳酸化促进的KLF4多梳抑制引发视网膜母细胞瘤中的糖酵解：组蛋白修饰之间的正反馈回路

IF 9.1 1区医学

Cancer letters Pub Date : 2025-05-16 DOI: 10.1016/j.canlet.2025.217804

Ludi Yang , Sipeng Zuo , Ruobing Jia , Xiang Gu , Qili Liao , Yu Hua , Shengfang Ge , Mengjia He , Jiayan Fan , Xuemei Tong , Tifei Yuan , Renbing Jia , Xianqun Fan , Peiwei Chai , Xuyang Wen

{"title":"Lactylation-boosted polycomb repression of KLF4 elicits glycolysis in retinoblastoma: A positive feedback circuit between histone modifications","authors":"Ludi Yang , Sipeng Zuo , Ruobing Jia , Xiang Gu , Qili Liao , Yu Hua , Shengfang Ge , Mengjia He , Jiayan Fan , Xuemei Tong , Tifei Yuan , Renbing Jia , Xianqun Fan , Peiwei Chai , Xuyang Wen","doi":"10.1016/j.canlet.2025.217804","DOIUrl":"10.1016/j.canlet.2025.217804","url":null,"abstract":"<div><div>The perturbation of histone modification homeostasis is a hallmark of oncogene activation and tumor suppressor gene silencing. Howbeit, the intricate interplay among diverse histone modifications in the context of tumorigenesis is not fully understood. Herein, we unveil a positive feedback mechanism involving lactylation and methylation of histones, which is instrumental in the oncogenic progression of retinoblastoma. First, we pinpointed that the selective upregulation of SUZ12 leads to the upregulation of H3K27me3 modification in retinoblastoma, which is attributed to heightened levels of histone lactylation. Notably, the targeted suppression of <em>SUZ12</em> has demonstrated significant therapeutic benefits in both <em>in vitro</em> and <em>in vivo</em> models of retinoblastoma. Furthermore, multi-omics analysis has identified Krüppel-like factor 4 (<em>KLF4</em>) as a key downstream effector of SUZ12. Mechanistically, SUZ12 is implicated in the enhancement of the H3K27me3 mark on the <em>KLF4</em> promoter, thereby repressing its transcription. Intriguingly, the downregulation of <em>KLF4</em> is associated with an upregulation of glycolysis and a concomitant accumulation of the onco-metabolite lactate, which in turn augments histone lactylation. In conclusion, we provide novel insights into the intricate interplay between lactylation and methylation of histones, shedding light on the epigenetic-metabolic reprogramming that underlies oncogene activation and tumor suppressor gene inactivation in cancer.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"625 ","pages":"Article 217804"},"PeriodicalIF":9.1,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090303","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}

引用次数: 0

Molecular profiling reveals the malignant potential in solid pseudopapillary neoplasms of the pancreas 分子图谱显示胰腺实性假乳头状肿瘤的恶性潜能

IF 9.1 1区医学

Cancer letters Pub Date : 2025-05-15 DOI: 10.1016/j.canlet.2025.217788

Jiayi Li , Huaijin Zheng , Xiang Zhang , Boju Pan , Junliang Lu , Liangrui Zhou , Taiping Zhang , Menghua Dai , Junchao Guo , Weibin Wang , Xianlin Han , Qiang Xu , Yuze Hua , Jorg Kleeff , Huanwen Wu , Zhiyong Liang , Qiaofei Liu , Quan Liao

{"title":"Molecular profiling reveals the malignant potential in solid pseudopapillary neoplasms of the pancreas","authors":"Jiayi Li , Huaijin Zheng , Xiang Zhang , Boju Pan , Junliang Lu , Liangrui Zhou , Taiping Zhang , Menghua Dai , Junchao Guo , Weibin Wang , Xianlin Han , Qiang Xu , Yuze Hua , Jorg Kleeff , Huanwen Wu , Zhiyong Liang , Qiaofei Liu , Quan Liao","doi":"10.1016/j.canlet.2025.217788","DOIUrl":"10.1016/j.canlet.2025.217788","url":null,"abstract":"<div><div>Solid pseudopapillary neoplasm of the pancreas (SPN) is a rare tumor primarily affecting middle-aged women, typically characterized by indolent behavior but occasionally demonstrating malignant potential through invasive growth and metastasis. To elucidate the molecular mechanisms driving this heterogeneity, a multi-omics approach was applied to analyze paired metastatic lesions, primary tumors, and normal pancreatic tissues. Methylation profiling via the Illumina Infinium Methylation EPIC BeadChip identified 2425 differentially methylated positions (DMPs) in metastatic versus primary lesions, with 798 DMPs conserved across both lesion types. Tyrosine kinases and cGMP-PKG signaling pathway were the most significantly enriched KEGG pathways involved in the DMPs. Transcriptomic analysis of invasive and non-invasive SPNs using NanoString revealed 99 differentially expressed genes (DEGs). Immunohistochemical validation confirmed elevated protein expression of LY96, IFI16, and GLUD1 in invasive cases. Circulating free DNA (cfDNA) sequencing did not detect genetic mutation in non-metastatic SPN, in contrast, 42.9 % positivity of genetic mutations were detected in metastatic SPNs. Tumor microenvironment analysis by using the GEO database, 850 K methylation sequencing, NanoString transcriptome, highlighted enriched immune-suppressive stromal components in aggressive tumors. These findings establish a molecular signature linking methylation dysregulation, transcriptomic alterations, liquid biopsy, and immune evasion to SPN progression, offering potential biomarkers for risk stratification and therapeutic targeting.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"625 ","pages":"Article 217788"},"PeriodicalIF":9.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144072669","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}

引用次数: 0

MLCK inhibition induces synthetic lethality in MYC-driven cancer MLCK抑制诱导myc驱动的癌症的合成致死性

IF 9.1 1区医学

Cancer letters Pub Date : 2025-05-15 DOI: 10.1016/j.canlet.2025.217803

Zhe Sun , Rui Wu , Xiaohui Liang , Tiezhu Shi , Yuan Zhang , Zelin Pan , Weidong Zhang , Xin Luan

{"title":"MLCK inhibition induces synthetic lethality in MYC-driven cancer","authors":"Zhe Sun , Rui Wu , Xiaohui Liang , Tiezhu Shi , Yuan Zhang , Zelin Pan , Weidong Zhang , Xin Luan","doi":"10.1016/j.canlet.2025.217803","DOIUrl":"10.1016/j.canlet.2025.217803","url":null,"abstract":"<div><div>The dysregulation of MYC is widely implicated in human cancers, yet MYC remains an ‘undruggable’ target. Here, we performed a CRISPR-based loss-of-function screen focusing on kinases, most of which are ‘druggable,’ to identify genes essential for MYC<sup>high</sup> but not MYC<sup>low</sup> cells. Using an isogenic pair of nonmalignant cells with and without ectopic MYC expression, we uncovered novel MYC synthetic lethal (MYC-SL) interactions, including Myosin Light-Chain Kinase (MLCK) as the most potent MYC-SL target. Inhibition of MLCK induced MYC-dependent cell death, significantly suppressing tumor growth in MYC-driven xenografts, the Apc<sup>Min/+</sup> mouse model of colon cancer, and the MYC-transgenic hepatocellular carcinoma (HCC) model, without apparent toxicity. This cell death is attributed to selective DNA damage and p53-mediated apoptosis. Mechanistically, MYC activation promotes nuclear accumulation of myosin II at stalled replication forks, where it resolves replication stress and supports survival. MLCK inhibition disrupts myosin II activity, leading to unresolved replication stress, DNA damage, and activation of the p53-mediated apoptosis pathway. Our findings suggest that targeting MLCK offers a promising therapeutic strategy for MYC-driven cancers.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"625 ","pages":"Article 217803"},"PeriodicalIF":9.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090213","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}

引用次数: 0

YAP/TAZ: An epitome of tumorigenesis YAP/TAZ：肿瘤发生的一个缩影。

IF 9.1 1区医学

Cancer letters Pub Date : 2025-05-15 DOI: 10.1016/j.canlet.2025.217806

Soumya Mukherjee, Emily A. Warden, Jianmin Zhang

{"title":"YAP/TAZ: An epitome of tumorigenesis","authors":"Soumya Mukherjee, Emily A. Warden, Jianmin Zhang","doi":"10.1016/j.canlet.2025.217806","DOIUrl":"10.1016/j.canlet.2025.217806","url":null,"abstract":"<div><div>Mounting evidence has demonstrated that the transcriptional coactivators Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), are the main effectors of the Hippo signal transduction pathway that is involved in multiple layered events in tumorigenesis. The role of YAP/TAZ in cancer development is critical in a context dependent manner. Overexpression of YAP/TAZ induces cell proliferation and is elevated in various cancers and many other malignancies. On the other hand, studies have shown YAP binds p73 to activate PML transcription in response to DNA damage and generate a DNA-damage-induced feedback loop. Intriguingly, at the genomic level, YAP/TAZ genes are rarely mutated in cancer, except in specific tumors. The central role of YAP/TAZ in driving tumorigenesis is attributed through diverse mechanisms, such as regulatory kinases, cellular mechano-transduction, epigenetic modification/alterations, post-translational modifications, protein -protein interaction and nucleo-cytoplasmic export import. The complex interplay among feedback loops and crosstalk between various signaling pathways portrays the dynamic nature of YAP/TAZ. Thus, a comprehensive understanding of how posttranslational modifications and nucleo-cytoplasmic traffic of YAP/TAZ dynamically regulate and control each other holds great promise for selectively targeting YAP/TAZ import and export for drug therapy.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"625 ","pages":"Article 217806"},"PeriodicalIF":9.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092864","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}

引用次数: 0