Cancer letters最新文献_第4页

Metabolic gatekeeper ACAD9 coordinates linoleic acid metabolism and redox homeostasis via mitochondrial complex I to drive ovarian cancer progression 代谢看门人ACAD9通过线粒体复合体I协调亚油酸代谢和氧化还原稳态，驱动卵巢癌进展。

IF 9.1 1区医学

Cancer letters Pub Date : 2025-07-05 DOI: 10.1016/j.canlet.2025.217903

Jia Li , Jie Shi , Jixuan Ding , Weiao Qu , Jianying Lv , Yuting Bai , Shuo Wang , Rui Zhou , Yanan Chen , Yanhua Liu , Wei Ding , Yongjun Piao , Yan Fan , Longlong Wang , Shuang Yang , Tong Li , Yi Shi

{"title":"Metabolic gatekeeper ACAD9 coordinates linoleic acid metabolism and redox homeostasis via mitochondrial complex I to drive ovarian cancer progression","authors":"Jia Li , Jie Shi , Jixuan Ding , Weiao Qu , Jianying Lv , Yuting Bai , Shuo Wang , Rui Zhou , Yanan Chen , Yanhua Liu , Wei Ding , Yongjun Piao , Yan Fan , Longlong Wang , Shuang Yang , Tong Li , Yi Shi","doi":"10.1016/j.canlet.2025.217903","DOIUrl":"10.1016/j.canlet.2025.217903","url":null,"abstract":"<div><div>Balancing high metabolic activity with redox homeostasis is crucial for cancer progression, particularly in high-grade serous ovarian cancer (HGSOC), which thrives in a lipid-rich environment abundance in free fatty acids, yet the key molecular regulators of this balance remain undefined. Through an <em>in vivo</em> genome-wide CRISPR/Cas9 knockout screen in an orthotopic ovarian cancer (OC) mouse model, we identify ACAD9 as a pivotal driver of OC progression, with its elevated expression correlating with poor patient prognosis. Multi-omics integration analysis and mechanism studies reveal ACAD9's dual role in maintaining OC metabolic homeostasis. ACAD9 preserves electron transport chain integrity and regulates linoleic acid (LA) metabolism to sustain energy production while mitigating oxidative stress. ACAD9 deficiency triggers mitochondrial respiratory collapse, inducing metabolic crisis marked by oxidative phosphorylation failure and reactive oxygen species (ROS) accumulation. Strikingly, under LA-enriched condition, ACAD9 loss redirects LA flux from β-oxidation toward membrane lipid biosynthesis, increasing polyunsaturated fatty acids incorporation. This membrane remodeling synergizes with ROS overload to create a “perfect storm” triggering ferroptosis. Our findings elucidate the dual metabolic guardianship of ACAD9 in OC, demonstrating its critical role in orchestrating mitochondrial respiration and lipid homeostasis to evade ferroptosis, which offer a potential target for the treatment of OC.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"630 ","pages":"Article 217903"},"PeriodicalIF":9.1,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574881","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

CEMIP2 sensitizes PDAC to chemotherapy through extracellular matrix remodeling by hyaluronan degradation CEMIP2通过透明质酸降解的细胞外基质重塑使PDAC对化疗敏感。

IF 9.1 1区医学

Cancer letters Pub Date : 2025-07-05 DOI: 10.1016/j.canlet.2025.217898

Na Yao , Yue Fu , Ting Wang , Jiejie Qin , Yizhi Cao , Minmin Shi , Fangfang Ma , Baiyong Shen , Lingxi Jiang

{"title":"CEMIP2 sensitizes PDAC to chemotherapy through extracellular matrix remodeling by hyaluronan degradation","authors":"Na Yao , Yue Fu , Ting Wang , Jiejie Qin , Yizhi Cao , Minmin Shi , Fangfang Ma , Baiyong Shen , Lingxi Jiang","doi":"10.1016/j.canlet.2025.217898","DOIUrl":"10.1016/j.canlet.2025.217898","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) ranks as third leading cause of cancer-related mortality, with chemoresistance progression driven by the desmoplastic extracellular matrix (ECM). Hyaluronic acid (HA), one of the major components of ECM, is notably enriched in PDAC. HA-based strategies, like lowering HA levels with a hyaluronidase, are worthy of experimental evidence for PDAC. Our previous work identified CEMIP2 (Cell migration inducing hyaluronidase 2) as a proteomic biomarker predictive of adjuvant chemotherapy response in PDAC, though its mechanistic role remains unclear. Herein, we observed that elevated CEMIP2 expression correlates with improved patient response to neoadjuvant and adjuvant chemotherapy. Using PDAC murine models, we reveal that CEMIP2 enhances gemcitabine efficacy through HA-dependent mechanisms involving drug delivery potentiation and vascular density modulation, attributable to its HA-degrading capacity. Consistent with this, CEMIP2 expression shows an inverse correlation with HA levels in clinical PDAC specimens, while low HA levels themselves associate with favorable treatment response and survival outcomes. Single-cell RNA sequencing (scRNA-seq) uncovered that CEMIP2 knockdown alters the tumor microenvironment (TME) by expanding cancer-associated fibroblast (CAF) populations. Both inflammatory (iCAF) and myofibroblast (myCAF) subtypes exhibited SPP1-CD44-mediated crosstalk with PDAC cells. Additionally, cytometry by time-of-flight (CyTOF) revealed that CEMIP2 depletion modulates the abundance and functional states of immune subsets, particularly tumor-associated macrophages (TAMs) and T cell populations. Collectively, our findings establish CEMIP2 as a critical regulator of chemotherapy response that reprograms the TME through HA degradation and ECM remodeling, providing novel insights into PDAC treatment resistance mechanisms.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"630 ","pages":"Article 217898"},"PeriodicalIF":9.1,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583094","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

CSNK2A1 confers gemcitabine resistance to pancreatic ductal adenocarcinoma via inducing autophagy. CSNK2A1通过诱导自噬赋予吉西他滨对胰腺导管腺癌的耐药性。

IF 9.1 1区医学

Cancer letters Pub Date : 2025-07-05 DOI: 10.1016/j.canlet.2025.217905

Marco Cordani, Min Li

引用次数: 0

Efficacy and safety of sunvozertinib monotherapy as first-line treatment in NSCLC patients with EGFR exon 20 insertion mutations: A phase 2, single-center trial Sunvozertinib单药治疗EGFR外显子20插入突变NSCLC患者的疗效和安全性：一项2期单中心试验

IF 9.1 1区医学

Cancer letters Pub Date : 2025-07-05 DOI: 10.1016/j.canlet.2025.217904

Yan Xu , Minjiang Chen , Xiaoxing Gao , Xiaoyan Liu , Jing Zhao , Wei Zhong , Mei Wang , Hongli Lang , Chingwan Yip , Mengzhao Wang

{"title":"Efficacy and safety of sunvozertinib monotherapy as first-line treatment in NSCLC patients with EGFR exon 20 insertion mutations: A phase 2, single-center trial","authors":"Yan Xu , Minjiang Chen , Xiaoxing Gao , Xiaoyan Liu , Jing Zhao , Wei Zhong , Mei Wang , Hongli Lang , Chingwan Yip , Mengzhao Wang","doi":"10.1016/j.canlet.2025.217904","DOIUrl":"10.1016/j.canlet.2025.217904","url":null,"abstract":"<div><div>Currently, no chemotherapy-free therapy is approved for the first-line treatment of non–small cell lung cancer (NSCLC) patients with <em>EGFR</em> exon 20 insertion mutations (exon20ins). Sunvozertinib is an oral <em>EGFR</em> tyrosine kinase inhibitor, which has been approved in China for ≥ second-line <em>EGFR</em> exon20ins NSCLC. We conducted a multi-group phase 2 study of sunvozertinib, WU-KONG15 (NCT05559645), to explore its antitumor efficacy in treatment-naïve <em>EGFR</em> exon20ins NSCLC (Group 4).</div><div>Sunvozertinib was administered at 200 mg once daily (QD). The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), duration of response (DoR), overall survival (OS), and safety. Exploratory endpoints included circulating tumor DNA (ctDNA) biomarkers.</div><div>As of January 15, 2025, 26 treatment-naïve patients with <em>EGFR</em> exon20ins NSCLC were enrolled and included in the efficacy analysis set. The median PFS was 10.1 months (95 % CI: 6.2, 13.9), with confirmed ORR of 73.1 % (95 % CI: 52.2, 88.4) and median DoR of 10.5 months (95 % CI: 7.2, 21.2). The estimated median OS was 23.1 months (95 % CI: 13.1, NE). A total of 99 patients were included in the safety analysis set. The median relative dose intensity was 98.2 %. The incidence of Grade ≥3 treatment-related adverse events was 35.4 %, including blood creatine phosphokinase increased (10.1 %), diarrhoea (8.1 %) and anaemia (8.1 %). Negativity of plasma <em>EGFR</em> exon20ins ctDNA correlated with better tumor response.</div><div>In conclusion, sunvozertinib monotherapy demonstrated significant and durable antitumor efficacy and was well-tolerated in treatment-naïve patients with <em>EGFR</em> exon20ins NSCLC, suggesting its potential as a favorable first-line treatment option.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"630 ","pages":"Article 217904"},"PeriodicalIF":9.1,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574880","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 "Combined inhibition of CDK4/6 and AKT is highly effective against the luminal androgen receptor (LAR) subtype of triple negative breast cancer" [604 (2024) 217219 1-12]. “联合抑制CDK4/6和AKT对三阴性乳腺癌的腔内雄激素受体（LAR）亚型非常有效”[604(2024)217219 1-12]的更正。

IF 9.1 1区医学

Cancer letters Pub Date : 2025-07-05 DOI: 10.1016/j.canlet.2025.217891

María Rosario Chica-Parrado, Gun Min Kim, Yasuaki Uemoto, Fabiana Napolitano, Chang-Ching Lin, Dan Ye, Emmanuel Bikorimana, Yisheng Fang, Kyung-Min Lee, Saurabh Mendiratta, Ariella B Hanker, Carlos L Arteaga

引用次数: 0

Corrigendum to "ASPH dysregulates cell death and induces chemoresistance in hepatocellular carcinoma"[Cancer Lett. 611 (2025) 217396]. “ASPH在肝细胞癌中失调细胞死亡和诱导化疗耐药”的更正[癌症杂志]. 611(2025)217396]。

IF 9.1 1区医学

Cancer letters Pub Date : 2025-07-03 DOI: 10.1016/j.canlet.2025.217892

Jingtao Li, Guocai Zhong, Fengli Hu, Yingnan Zhang, Xiaohang Ren, Zongwen Wang, Shuoheng Ma, Qiankun Zhu, Junwei Li, Shicong Zeng, Yao Zhang, Ting Wang, Qiushi Lin, Xiaoqun Dong, Bo Zhai

引用次数: 0

Corrigendum to "Liver fibrosis promotes immune escape in hepatocellular carcinoma via GOLM1-mediated PD-L1 upregulation" [Cancer Letters 513 (2021) 14-25]. “肝纤维化通过golm1介导的PD-L1上调促进肝细胞癌的免疫逃逸”的更正[Cancer Letters 513(2021) 14-25]。

IF 9.1 1区医学

Cancer letters Pub Date : 2025-07-03 DOI: 10.1016/j.canlet.2025.217899

Meng-Yun Ke, Tao Xu, Yi Fang, Yuan-Peng Ye, Zhi-Jin Li, Feng-Gang Ren, Shao-Ying Lu, Xu-Feng Zhang, Rong-Qian Wu, Yi Lv, Jian Dong

引用次数: 0

Endoplasmic reticulum stress-driven nucleotide catabolism fuels prostate cancer 内质网应激驱动的核苷酸分解代谢促进前列腺癌。

IF 9.1 1区医学

Cancer letters Pub Date : 2025-07-03 DOI: 10.1016/j.canlet.2025.217888

Ke Deng , Nora Pällmann , Marte Livgård , Wanja Kildal , Manohar Pradhan , Ladan Fazli , Paul S. Rennie , Yang Jin , Fahri Saatcioglu , Omer F. Kuzu

{"title":"Endoplasmic reticulum stress-driven nucleotide catabolism fuels prostate cancer","authors":"Ke Deng , Nora Pällmann , Marte Livgård , Wanja Kildal , Manohar Pradhan , Ladan Fazli , Paul S. Rennie , Yang Jin , Fahri Saatcioglu , Omer F. Kuzu","doi":"10.1016/j.canlet.2025.217888","DOIUrl":"10.1016/j.canlet.2025.217888","url":null,"abstract":"<div><div>Endoplasmic reticulum (ER) stress is a critical regulator of cancer cell metabolism and survival. In this study, we elucidate the coordinated roles of two key ER stress mediators, Activating Transcription Factor 4 (ATF4) and X-box Binding Protein 1 spliced (XBP1s), in regulating purine homeostasis in prostate cancer (PCa) cells. We demonstrate that ATF4 directly upregulates Molybdenum Cofactor Sulfurase (<em>MOCOS</em>), a key enzyme in purine catabolism, while XBP1s induces the expression of xanthine dehydrogenase (<em>XDH</em>), the principal MOCOS target in this pathway. Knockdown of MOCOS significantly impairs PCa cell proliferation as well as prostatosphere and colony formation in vitro, and inhibits tumor growth in preclinical mouse models of PCa. Mechanistically, MOCOS suppression leads to purine accumulation, disrupts pyrimidine synthesis, and causes nucleotide imbalance, resulting in replication fork stalling. This imbalance is also accompanied by a compromised glutathione-mediated antioxidant response, rendering the cells more susceptible to DNA damage. Importantly, targeting XDH, either genetically or biochemically, also significantly hinders PCa cell growth. Collectively, our data highlight the pivotal role of ER stress-mediated purine homeostasis in sustaining PCa cell growth.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"630 ","pages":"Article 217888"},"PeriodicalIF":9.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567137","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

PD-L1 delactylation-promoted nuclear translocation accelerates liver cancer growth through elevating SQLE transcription activity PD-L1去乙酰化促进的核易位通过提高SQLE转录活性加速肝癌的生长

IF 9.1 1区医学

Cancer letters Pub Date : 2025-07-02 DOI: 10.1016/j.canlet.2025.217901

Xue Wang , Ye Li , Yanxin Tang , Zhiyu Liu , Yuan Liu , Xueli Fu , Shiman Guo , Jiaqi Ma , Fangyuan Ma , Zhitu Zhu , Weiying Zhang , Lihong Ye

{"title":"PD-L1 delactylation-promoted nuclear translocation accelerates liver cancer growth through elevating SQLE transcription activity","authors":"Xue Wang , Ye Li , Yanxin Tang , Zhiyu Liu , Yuan Liu , Xueli Fu , Shiman Guo , Jiaqi Ma , Fangyuan Ma , Zhitu Zhu , Weiying Zhang , Lihong Ye","doi":"10.1016/j.canlet.2025.217901","DOIUrl":"10.1016/j.canlet.2025.217901","url":null,"abstract":"<div><div>Programmed death-ligand 1 (PD-L1), a critical immune checkpoint ligand, is overexpressed in several malignancies. The newly identified protein posttranslational modification lactylation, occurring on lysine residues, is extensively involved in various biological processes. However, PD-L1 lactylation and its role in tumorigenesis remain unclear. In this study, we discover that lactylation of PD-L1 suppresses liver cancer growth by inhibiting cholesterol synthesis. Acetyltransferase E1A-binding protein p300 (p300) catalyzes the lactylation of PD-L1 at the lysine 189 residue (K189). Histone deacetylase 2-dependent delactylation of PD-L1 K189 promotes vimentin-mediated nuclear translocation of PD-L1. Functionally, PD-L1 K189 delactylation accelerates liver cancer growth both <em>in vitro</em> and <em>in vivo</em> by facilitating cholesterol production. Clinically, an antibody against PD-L1 K189 lactylation reveals that PD-L1 delactylation is positively associated with the progression of liver cancer histological grade. Mechanistically, PD-L1 K189 delactylation upregulates SQLE, a rate-limiting enzyme in cholesterol biosynthesis, by increasing <em>SQLE</em> transcription activity <em>via</em> the transcription factor YY1. Therefore, our findings demonstrate that lactylation-dependent regulation of PD-L1 promotes liver cancer growth.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"630 ","pages":"Article 217901"},"PeriodicalIF":9.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144557588","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 "Targeting doublecortin-like kinase 1 reveals a novel strategy to circumvent chemoresistance and metastasis in ovarian cancer" [Cancer Lett. 2023 Dec 1;578:216437]. “靶向双皮质素样激酶1揭示了规避卵巢癌化疗耐药和转移的新策略”的更正[cancer Lett. 2023 Dec 1;578:216437]。

IF 9.1 1区医学

Cancer letters Pub Date : 2025-07-02 DOI: 10.1016/j.canlet.2025.217889

Samrita Dogra, Sugantha Priya Elayapillai, Dongfeng Qu, Kamille Pitts, Alexander Filatenkov, Courtney W Houchen, William L Berry, Katherine Moxley, Bethany N Hannafon

引用次数: 0