Cancer letters最新文献

{"title":"hnRNPLL regulates MYOF alternative splicing and correlates with early metastasis in pancreatic ductal adenocarcinoma.","authors":"Xianghan Chen, Ruining Gong, Lili Wang, Ke Lei, Xiaolan Liu, Jigang Wang, Mingyue Sun, Ashok Kumar Saluja, Qian Yu, He Ren","doi":"10.1016/j.canlet.2024.217436","DOIUrl":"https://doi.org/10.1016/j.canlet.2024.217436","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer known for its high rate of early metastasis, necessitating the discovery of the underlying mechanisms. Herein, we report that heterogeneous nuclear ribonucleoprotein L-like (hnRNPLL) expression significantly increases at the invasion forefront in PDAC and is associated with early metastasis and poor prognosis. Our findings revealed that hnRNPLL knockdown resulted in extensive exon skipping (ES) events. In particular, we identified myoferlin (MYOF), a member of the ferlin family involved in membrane processes, as a functional splicing target of hnRNPLL. hnRNPLL depletion stimulates MYOF exon 17 retention to reduce the short isoform of MYOF (MYOFb) and inhibit metastasis. In contrast, hnRNPLL or MYOFb overexpression promoted pancreatic cancer cell migration and invasion. These results suggest that hnRNPLL is a critical factor for early PDAC metastasis. hnRNPLL and MYOFb may be potential therapeutic targets for PDAC.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217436"},"PeriodicalIF":9.1,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913850","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":"Vaccines targeting p53 mutants elicit anti-tumor immunity.","authors":"Dafei Chai, Xu Wang, Chunmei Fan, Junhao Wang, Jing Ming Lim, Xinfang Yu, Ken H Young, Yong Li","doi":"10.1016/j.canlet.2024.217421","DOIUrl":"https://doi.org/10.1016/j.canlet.2024.217421","url":null,"abstract":"<p><p>The p53 tumor suppressor is commonly mutated in cancer; however, there are no effective treatments targeting p53 mutants. A DNA vaccine gWIZ-S237G targeting the p53 S237G mutant, which is highly expressed in A20 murine tumor cells, was developed and administered intramuscularly via electroporation, either alone or in combination with PD1 blockade. The anti-p53-S237G immunization elicited a robust protective response against subcutaneous A20 tumors and facilitated the infiltration of immune cells including CD8⁺ T cells, NK cells, and DCs. The vaccine enhanced the induction and maturation of CD11c⁺, CD103⁺CD11c⁺, and CD8⁺CD11c⁺ cells, which in turn promoted tumor-specific antibody production, as well as Th1 and CD8⁺ T cell-mediated immune responses. Several antigenic epitopes of p53-S237G effectively stimulated multifunctional CD8⁺ T cells to secrete IFN-γ and TNF-α. The vaccine showed long-term anti-tumor effects that were dependent on memory CD8⁺ T cells. Furthermore, the anti-p53-S237G vaccine exhibited significant protective efficacy in the A20 liver metastasis models. When combined with PD-1 inhibition, the vaccine showed superior inhibition of tumor growth and liver metastasis. Targeting p53 mutants by vaccination represents a potential precision medicine strategy against cancers harboring p53 mutations.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217421"},"PeriodicalIF":9.1,"publicationDate":"2024-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909458","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":"Immunochemotherapy plus radiotherapy versus immunochemotherapy alone as first-line treatment for treatment-naïve, advanced esophageal squamous cell carcinoma (AEC-ICR-1st): A multi-center cohort study.","authors":"Jiacheng Li, Xiaofeng Wang, Jianzhong Cao, Chengcheng Fan, Qin Xiao, Zhunhao Zheng, Wenyan Gao, Xiao Liu, Peixin Feng, Fang Liu, Shuyu Ouyang, Tian Zhang, Xi Chen, Zhiyong Yuan, Qingsong Pang, Ping Wang, Qifeng Wang, Wencheng Zhang","doi":"10.1016/j.canlet.2024.217411","DOIUrl":"10.1016/j.canlet.2024.217411","url":null,"abstract":"<p><p>Immunochemotherapy is Currently the standard first-line treatment for advanced esophageal squamous cell carcinoma (ESCC). However, its prognosis remains unsatisfactory. We aimed to evaluate the efficacy and safety of immunochemotherapy plus radiotherapy (ICR) compared with immunochemotherapy (IC) alone as a first-line treatment for advanced ESCC. This multicenter cohort study was conducted across five cancer centers (NCT06190652). We evaluated the outcomes in patients with advanced ESCC who received first-line therapy of IC, with or without radiotherapy (RT), between 2018 and 2023. Propensity score matching (PSM) was performed to control for potential confounders. Sensitivity analysis was conducted to evaluate the robustness of the results. Overall, 23,641 patients were screened, and 702 patients were finally eligible. 270 patients included in ICR cohort, and 432 patients in IC alone cohort. Both before and after PSM, the ICR cohort had a longer median OS compared to IC alone cohort (20.4 versus 16.8 months, P = 0.001; 21.3 versus 17.5 months, P = 0.008; respectively); multivariate analysis further supported that RT was associated with a better OS (HR: 0.695, 95%CI: 0.558-0.867, P = 0.001; HR: 0.729, 95%CI: 0.561-0.947, P = 0.018; respectively). Exploratory analysis revealed that the survival benefits were most pronounced in the subgroup that received IC concurrently combined with definitive dose RT to the primary tumor, with a median OS of 23.6 months (HR: 0.515, 95%CI: 0.308-0.862, P = 0.011) and PFS of 14.4 months (HR: 0.567, 95%CI: 0.370-0.870, P = 0.009). The grade ≥3 treatment-related adverse events (TRAEs) were esophagitis (4.10 % versus 0.41 %; P = 0.006), anemia (6.97 % versus 1.64 %; P = 0.004), leukopenia (12.70 % versus 6.56 %; P = 0.021) and lymphopenia (38.52 % versus 4.92 %, P < 0.001) in the ICR and IC cohorts. The addition of RT to IC as a first-line treatment for advanced ESCC could bring benefits, and was well-tolerated.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217411"},"PeriodicalIF":9.1,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906640","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":"Oncogenic HJURP enhancer promotes the aggressive behavior of triple-negative breast cancer in association with p53/E2F1/FOXM1-axis.","authors":"Yunlu Jia, Yongxia Chen, Ming Chen, Mengye He, Suzhen Xu, Han Li, Xuanyi Lin, Linbo Wang, Jichun Zhou, Peng Shen, Xiao Luo, Xiaochen Zhang, Jian Ruan","doi":"10.1016/j.canlet.2024.217423","DOIUrl":"https://doi.org/10.1016/j.canlet.2024.217423","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer, lacking effective targeted therapies and presenting with a poor prognosis. In this study, we utilized the epigenomic landscape, TCGA database, and clinical samples to uncover the pivotal role of HJURP in TNBC. Our investigation revealed a strong correlation between elevated HJURP expression and unfavorable prognosis, metastatic progression, and late-stage of breast cancer. RNA-seq analysis indicated that HJURP silencing suppressed transcriptional signatures associated with malignant phenotypes of TNBC, thereby inhibiting cell proliferation, migration, invasion, epithelial-to-mesenchymal transition (EMT), and promoting apoptosis. Knockdown of HJURP impaired the growth of MDA-MB231-engrafted tumors, reducing KI67 and HJURP expression in the shHJURP group. Publicly available datasets showed differential expression of HJURP in TNBC cells harboring mutant p53 (mutp53) compared to those with wild-type p53 (wtp53), highlighting a potential mechanism underlying TNBC's aggressiveness. Mechanistically, we established that loss or mutation of wtp53 enhances HJURP expression, whereas wtp53 accumulation restrains HJURP transcription. We elucidated a regulatory axis where wtp53 positively modulates the transcription factors FOXM1 and E2F1, which form a complex with H3K27ac to bind preferentially to the HJURP enhancer, driving its transcription. CRISPR interference targeting the enhancer region resulted in diminished HJURP expression and phenotypes reminiscent of HJURP knockdown, accompanied by reduced binding of E2F1, FOXM1, and H3K27ac to the enhancer. In a translational perspective, we found marked decreases in survival of breast cancer patients expressing high HJURP levels carrying wtp53. Collectively, our findings identify enhancer-driven HJURP as a pivotal molecular bypass that suppresses the tumor-suppressive and pro-apoptotic effects of wtp53. Targeting HJURP presents a compelling therapeutic strategy to inhibit tumor proliferation, metastasis, and invasiveness specifically p53-mutant TNBC.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217423"},"PeriodicalIF":9.1,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906641","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":"An emerging aspect of cancer neuroscience: A literature review on chemotherapy-induced peripheral neuropathy.","authors":"Zhirui Tao, Zhiqin Chen, Xiaochen Zeng, Jiujie Cui, Ming Quan","doi":"10.1016/j.canlet.2024.217433","DOIUrl":"10.1016/j.canlet.2024.217433","url":null,"abstract":"<p><p>The nervous system governs both ontogeny and oncology. Foundational discoveries have clarified the direct communication of neurotransmitters with tumors and indirect interactions through neural effects on the immune system and the tumor microenvironment. Meantime, the nervous system is susceptible to cancer and its treatment. Chemotherapy-induced peripheral neuropathy (CIPN) is the most common side effects that significantly reduce the efficacy of anti-cancer treatment and patients' quality of life by leading to dose reduction or early cessation of chemotherapy. However, there are no effective strategies to reverse or treat CIPN. A better understanding of the mechanisms is expected to enable the development of the next generation of therapies. Here, we summarize the recent important studies on clinical manifestations, risk factors, prediction, pathogenesis, prevention, and treatment of CIPN. We also provide perspectives and insights regarding the rationales of bidirectional interactions between cancer and the nervous system.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217433"},"PeriodicalIF":9.1,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906639","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":"Tumor-derived CCL15 regulates RNA m⁶A methylation in cancer-associated fibroblasts to promote hepatocellular carcinoma growth.","authors":"Chaomin Wang, Dong Dong, Na Zhao, Yang Liu, Changsen Bai, Jialei Hua, Ranliang Cui, Xi Wei, Ting Zhao, Ning Ji, Shuaini Yang, Jie Zhao, Huikai Li, Yueguo Li","doi":"10.1016/j.canlet.2024.217420","DOIUrl":"https://doi.org/10.1016/j.canlet.2024.217420","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a lethal malignancy characterized by rapid growth. The interaction between tumor cells and cancer-associated fibroblasts (CAFs) significantly influences HCC progression. CCL15, a CC chemokine family member, is predominantly expressed in HCC and strongly correlates with tumor size, indicating its critical role in HCC growth. However, previous studies suggest that CCL15 does not directly stimulate cancer cell proliferation. The specific role and mechanism of CCL15 in HCC proliferation remain unknown. Here, we identified that CCL15 was predominantly overexpressed by HCC cells through single-cell RNA sequencing data and immunofluorescence. We discovered that CCL15 promotes HCC growth by stimulating the crosstalk between HCC cells and CAFs via CCR1 signaling, as evidenced by co-culture assays, organoid models, and allograft models. Mechanistically, CCL15 induced the expression of FTO in CAFs through the STAT3 pathway. By m⁶A sequencing and RNA sequencing, we found that CEBPA mRNA, a transcription factor regulating CXCL5 expression, was a target of FTO. CXCL5, secreted by CAFs, activated the CXCR2 receptor on HCC cells and enhanced their proliferation. Notably, we found that interfering with CCL15 signaling using a neutralizing antibody attenuated HCC growth in heterotypic co-injection and patient-derived xenograft murine models. Finally, CXCL5 also upregulated CCL15 expression in HCC cells by modulating P53 expression through MDM2, forming a positive feedback loop. Our study unveiled CCL15 as a key mediator in HCC progression, facilitating communication between HCC cells and CAFs. This highlights a novel regulatory axis in HCC and suggests that targeting CCL15 could be a potential therapeutic strategy.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217420"},"PeriodicalIF":9.1,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902604","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":"Corrigendum to \"Cellular dynamics of tumor microenvironment driving immunotherapy resistance in non-small-cell lung carcinoma\" [Cancer Lett. 604 (2024) 217272].","authors":"Shujie Huang, Jeff Yat-Fai Chung, Chunjie Li, Yi Wu, Guibin Qiao, Ka-Fai To, Patrick Ming-Kuen Tang","doi":"10.1016/j.canlet.2024.217425","DOIUrl":"https://doi.org/10.1016/j.canlet.2024.217425","url":null,"abstract":"","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217425"},"PeriodicalIF":9.1,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892269","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":"RNF5 exacerbates steatotic HCC by enhancing fatty acid oxidation via the improvement of CPT1A stability.","authors":"Xi Chen, Yang-Wen-Qing Zhang, Hui Ren, Caixia Dai, Minghe Zhang, Xiaomian Li, Kequan Xu, Jinghua Li, Yi Ju, Xiaoyu Pan, Peng Xia, Weijie Ma, Wenzhi He, Tiangen Wu, Yufeng Yuan","doi":"10.1016/j.canlet.2024.217415","DOIUrl":"https://doi.org/10.1016/j.canlet.2024.217415","url":null,"abstract":"<p><p>Non-alcoholic fatty liver disease (NAFLD) is expected to become the leading risk factor for liver cancer, surpassing viral hepatitis. Unlike viral hepatitis-related hepatocellular carcinoma (HCC), the role of excessive nutrient supply in steatotic HCC is not well understood, hindering effective prevention and treatment strategies. Therefore, it is crucial to identify key molecules in the pathogenesis of steatotic HCC, investigate changes in metabolic reprogramming due to excessive fatty acid (FA) supply, understand its molecular mechanisms, and find potential therapeutic targets. Trans-species transcriptome analysis identified Ring Finger Protein 5 (RNF5) as a critical regulator of steatotic HCC. RNF5 upregulation is associated with poor prognosis in steatotic HCC compared to canonical HCC. In vitro and in vivo studies showed that RNF5 exacerbates HCC in the presence of additional FA supply. Lipidomics and transcriptome analyses revealed that RNF5 significantly increases carnitine palmitoyltransferase 1A (CPT1A) mRNA levels and is positively correlated with fatty acid oxidation (FAO). Protein interaction analysis demonstrated that RNF5 promotes K63-type ubiquitination of insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1), enhancing CPT1A mRNA stabilization through m6A modification. Additionally, peroxisome proliferator-activated receptor gamma (PPARγ) was found to activate RNF5 expression specifically in HCC cells. Mechanistically, excessive exogenous FAs reorganize FA metabolism in HCC cells, worsening steatotic HCC via the PPARγ-RNF5-IGF2BP1-CPT1A axis. This study highlights a distinct FA metabolism pattern in steatotic HCC, providing valuable insights for potential therapeutic targets.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217415"},"PeriodicalIF":9.1,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902584","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":"NSUN2-Mediated R-loop Stabilization as a Key Driver of Bladder Cancer Progression and Cisplatin Sensitivity.","authors":"Yuqing Wu, Yufan Ying, Fenghao Zhang, Xuan Shu, Zhixiang Qi, Jiaming Wang, Zixiang Liu, Yijie Tang, Jiazhu Sun, Jiahe Yi, Dingheng Lu, Shen Lin, Sida Hao, Xueyou Ma, Jiangfeng Li, Xiao Wang, Liping Xie, Xiangyi Zheng","doi":"10.1016/j.canlet.2024.217416","DOIUrl":"https://doi.org/10.1016/j.canlet.2024.217416","url":null,"abstract":"<p><p>R-loops are critical structures that play pivotal roles in regulating genomic stability and modulating gene expression. This study investigates the interactions between the 5-methylcytosine (m⁵C) methyltransferase NOP2/Sun RNA methyltransferase 2 (NSUN2) and R-loops in the transcriptional dynamics and damage repair process of bladder cancer (BCa) cells. We observed markedly elevated levels of R-loops in BCa cells relative to normal urothelial cells. NSUN2 was identified as a regulator of R-loops, acting to bind and stabilize their structure through a process dependent on its m⁵C catalytic activity. The histone methyltransferase Enhancer of Zeste Homolog 2 (EZH2) was found to interact with NSUN2. Our results demonstrated that NSUN2 facilitates the epigenetic silencing of the tumor suppressor gene PR Domain Zinc Finger Protein 11 (PRDM11) by recruiting EZH2, thereby advancing the progression of BCa. Furthermore, NSUN2 knockdown sensitizes tumors to cisplatin, resulting in reduced tumor growth and increased DNA damage levels, which was associated with reduced recruitment of MRE11 to damage sites, thereby impairing homologous recombination repair. These findings enhance our understanding of BCa pathogenesis and identify new potential targets for therapeutic intervention.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217416"},"PeriodicalIF":9.1,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892316","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":"Disulfiram impairs USP21-mediated MOF-K257 deubiquitination to inhibit esophageal squamous cell carcinoma progression.","authors":"Lingxiao Yang, Huacong Sui, Yi Ding, Yilin Zhu, Xiangqing Song, Yifan Zhang, Guangyan Fan, Jiaxu Wang, Xiujie Cui, Yunfeng Jiang, Shuyong Zhao, Yilang Hong, Ning Mu, Zhongxian Tian, Yunpeng Zhao, Peichao Li, Xiaogang Zhao","doi":"10.1016/j.canlet.2024.217419","DOIUrl":"10.1016/j.canlet.2024.217419","url":null,"abstract":"<p><p>Disulfiram (DSF), primarily applied in the therapy for alcohol addiction, has been demonstrated to possess the promising capability of anti-tumor in many human cancers, including esophageal squamous cell carcinoma (ESCC). To date, almost all studies about DSF in ESCC are focusing on investigating either drug combinations or nanoparticle-based delivery systems. However, the exact molecular mechanisms mediating the response to DSF in ESCC are totally unknown. An increasing number of studies reported that aberrant expression of acetylation-related genes is closely involved in regulating the response of cancer cells to anti-tumor drugs. Here, we defined DSF-sensitive and -resistant cells by measuring the half-maximal inhibitory concentration (IC₅₀) of DSF in four ESCC cell lines, followed by detecting the protein expression of nine dysregulated histone acetyltransferase (HAT) genes in ESCC. Our results demonstrate that MOF is responsible for the sensitivity to DSF in ESCC cells. Consistently, DSF treatment markedly abolished MOF-driving ESCC progression and Wnt/β-Catenin signaling activation. Interestingly, DSF decreased MOF protein expression via the ubiquitin-proteasome system. Further exploration verified the essential role of USP21, among three candidates (USP2, USP21, and USP10), in DSF-mediated MOF protein levels. Mechanistically, USP21 binds to MOF protein and decreases the ubiquitination of its K257 site, while DSF notably impedes MOF-mediated ESCC malignant progression and Wnt/β-Catenin signaling activation by blocking USP21-governed MOF-K257 deubiquitination. In conclusion, our study elucidates the USP21/MOF-K257 axis regulating the response to DSF in ESCC, which provides novel and key evidence for the clinical application of DSF in individualized therapy for ESCC patients.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217419"},"PeriodicalIF":9.1,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892271","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}