Cancer letters最新文献

{"title":"Anoikis resistance in Cancer: Mechanisms, therapeutic strategies, potential targets, and models for enhanced understanding","authors":"Pallab Shaw ,&nbsp;Arpan Dey Bhowmik ,&nbsp;Mohan Shankar Gopinatha Pillai ,&nbsp;Nathan Robbins ,&nbsp;Shailendra Kumar Dhar Dwivedi ,&nbsp;Geeta Rao","doi":"10.1016/j.canlet.2025.217750","DOIUrl":"10.1016/j.canlet.2025.217750","url":null,"abstract":"<div><div>Anoikis, defined as programmed cell death triggered by the loss of cell-extracellular matrix (ECM) and cell-cell interactions, is crucial for maintaining tissue homeostasis and preventing aberrant cell migration. Cancer cells, however, display anoikis resistance (AR) which in turn enables cancer metastasis. AR results from alterations in apoptotic signaling, metabolic reprogramming, autophagy modulation, and epigenetic changes, allowing cancer cells to survive in detached conditions. In this review we describe the mechanisms underlying both anoikis and AR, focusing on intrinsic and extrinsic pathways, disrupted cell-ECM interactions, and autophagy in cancer. Recent findings (i.e., between 2014 and 2024) on epigenetic regulation of AR and its role in metastasis are discussed. Therapeutic strategies targeting AR, including chemical inhibitors, are highlighted alongside a network analysis of 122 proteins reported to be associated with AR which identifies 53 hub proteins as potential targets. We also evaluate <em>in vitro</em> and <em>in vivo</em> models for studying AR, emphasizing their role in advancing metastasis research. Our overall goal is to guide future studies and therapeutic developments to counter cancer metastasis.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"624 ","pages":"Article 217750"},"PeriodicalIF":9.1,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899867","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":"Hormonal and neuronal interactions shaping the brain metastatic microenvironment","authors":"Stephen Shovlin ,&nbsp;Leonie S. Young ,&nbsp;Damir Varešlija","doi":"10.1016/j.canlet.2025.217739","DOIUrl":"10.1016/j.canlet.2025.217739","url":null,"abstract":"<div><div>Metastatic progression drives the majority of cancer-related fatalities, and involvement of the central nervous system (CNS) poses especially formidable challenges to patients and clinicians. Brain metastases (BrM), commonly originate from lung, breast and melanoma cancers, and carry disproportionately poor outcomes. Although therapeutic advances have extended survival for many extracranial tumors, BrM incidence continues to climb—underscoring critical knowledge gaps in understanding the unique biology of tumor colonization in the CNS. While definitive evidence remains limited, a growing focus on cancer neuroscience—especially regarding hormone dependent cancer cells in the brain—has begun to reveal that factors normally regulated by sex steroids and neurosteroids may similarly influence the specialized metastatic microenvironment in the CNS. Steroid hormones can permeate the blood-brain barrier (BBB) or be synthesized <em>de novo</em> by astrocytes and other CNS-resident cells, potentially influencing processes such as inflammation, synaptic plasticity, and immune surveillance. However, how these hormonal pathways are co-opted by disseminated cancer cells remains unclear. Here, we review the complex hormonal landscape of the adult brain and examine how neuroendocrine–immune interactions, often regulated by sex hormones, may support metastatic growth. We discuss the interplay between systemic hormones, local steroidogenesis, and tumor adaptation to identify novel therapeutic opportunities.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"624 ","pages":"Article 217739"},"PeriodicalIF":9.1,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891596","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-associated Schwann cells as new therapeutic target in non-neurological cancers","authors":"Leyi Huang ,&nbsp;Ge Qi ,&nbsp;Guangyao Chen ,&nbsp;Jinxin Duan ,&nbsp;Cao Dai ,&nbsp;Yanan Lu ,&nbsp;Quanbo Zhou","doi":"10.1016/j.canlet.2025.217748","DOIUrl":"10.1016/j.canlet.2025.217748","url":null,"abstract":"<div><div>Cancer neuroscience, a burgeoning field, investigates the complex interactions between cancer and the nervous system, emphasizing how cancer cells exploit neuronal components for growth and metastasis. Tumor-associated Schwann cells (TASc) have emerged as crucial players in the progression of highly innervated cancers, highlighting the intricate relationship between the tumor microenvironment (TME) and the nervous system. This review concludes how TASc, as the most abundant glial cell in the peripheral nervous system, contribute to tumor growth, metastasis, and the remodeling of the TME. Acting similarly to reactive astrocytes in the central nervous system, TASc are implicated in driving perineural invasion (PNI), a distinctive cancer progression pathway facilitating tumor infiltration and metastasis. These TASc not only contribute indirectly to pain but also promote tumor recurrence and poor prognosis. Intrinsic to their role, TASc exhibit unique gene expression profiles and phenotypic transformations, shifting from myelinating to non-myelinating states, thereby actively participating in metastasis and the remodeling of the tumor microenvironment. Targeting TASc represents a novel and promising therapeutic strategy in non-neurological cancers, offering new avenues for clinical intervention.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"624 ","pages":"Article 217748"},"PeriodicalIF":9.1,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143895182","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 “MED27 promotes melanoma growth by targeting AKT/MAPK and NF/κB/iNOS signaling pathway” [Cancer Lett. 373(1) (2016) 77-87 PMID 26797421]","authors":"Ranran Tang ,&nbsp;Xiangdong Xu ,&nbsp;Wenjing Yang ,&nbsp;Wendan Yu ,&nbsp;Shuai Hou ,&nbsp;Yang Xuan ,&nbsp;Zhipeng Tang ,&nbsp;Shilei Zhao ,&nbsp;Yiming Chen ,&nbsp;Xiangsheng Xiao ,&nbsp;Wenlin Huang ,&nbsp;Wei Guo ,&nbsp;Man Li ,&nbsp;Wuguo Deng","doi":"10.1016/j.canlet.2025.217717","DOIUrl":"10.1016/j.canlet.2025.217717","url":null,"abstract":"","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"623 ","pages":"Article 217717"},"PeriodicalIF":9.1,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859191","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":"Cancer stem cells and tumor-associated macrophages: Interactions and therapeutic opportunities","authors":"Haitao Yuan ,&nbsp;Yun Qiu ,&nbsp;Zijie Mei,&nbsp;Jiaqing Liu,&nbsp;Lingna Wang,&nbsp;Kaiqing Zhang,&nbsp;Huicong Liu,&nbsp;Fangfang Zhu","doi":"10.1016/j.canlet.2025.217737","DOIUrl":"10.1016/j.canlet.2025.217737","url":null,"abstract":"<div><div>Cancer stem cells (CSCs) depend on the tumor microenvironment (TME) to sustain their stem-like properties by recruiting monocytes and reprogramming them into tumor-associated macrophages (TAMs), which in turn promote tumor progression. This review explores CSC-TAM interactions, emphasizing how CSCs drive monocyte recruitment and TAM polarization. We discuss how TAMs enhance CSC stemness and niche maintenance through chemokines, cytokines, exosome-mediated miRNA transfer, direct interactions, and extracellular matrix (ECM) remodeling. Furthermore, we examine therapeutic strategies targeting TAMs, including inhibiting TAM differentiation, reprogramming TAM polarization, and leveraging immune checkpoint blockade and CAR-macrophage immunotherapy to improve cancer treatment outcomes.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"624 ","pages":"Article 217737"},"PeriodicalIF":9.1,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891597","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":"Extracellular Vesicles: Hermes between cancers and lymph nodes","authors":"Lei-Ming Cao ,&nbsp;Yu-Zhong Qiu ,&nbsp;Zi-Zhan Li ,&nbsp;Guang-Rui Wang ,&nbsp;Yao Xiao ,&nbsp;Han-Yue Luo ,&nbsp;Bing Liu ,&nbsp;Qiuji Wu ,&nbsp;Lin-Lin Bu","doi":"10.1016/j.canlet.2025.217735","DOIUrl":"10.1016/j.canlet.2025.217735","url":null,"abstract":"<div><div>Cancer is one of the main causes of death and a major obstacle to increasing life expectancy in all countries of the world. Lymph node metastasis (LNM) of in cancer patients indicates poor prognosis and it is an important indication to determine the therapeutic regime. Therefore, more attention should be given to the molecular mechanics of tumor lymphangiogenesis and LNM. Extracellular vesicles (EVs) are nanoscale cargo-bearing membrane vesicles that can serve as key mediators for the intercellular communication. Like Hermes, the messenger of the Greek gods, EVs can be secreted by tumor cells to regulate the LNM process. Many evidence has proved the clinical correlation between EVs and LNM in various cancer types. EVs plays an active role in the process of metastasis by expressing its connotative molecules, including proteins, nucleic acids, and metabolites. However, the clear role of EVs in the process of cancer LNM has not been thoroughly studied yet. In this review, we will summarize the clinical and mechanical findings of EVs regulating role on cancer LNM, and discuss the advanced modification of the research proposal. We propose the “PUMP” principle of EVs in LNM, including Preparation, Unleash, Migration, and Planting.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"623 ","pages":"Article 217735"},"PeriodicalIF":9.1,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864489","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":"Isoliquiritigenin reduces brain metastasis by circNAV3-ST6GALNAC5-EGFR axis in triple-negative breast cancer","authors":"Yi Xie ,&nbsp;Jindong Xie ,&nbsp;Guoxian Huang ,&nbsp;Jinhui Zhang ,&nbsp;Cailu Song ,&nbsp;Yongzhou Luo ,&nbsp;Hailin Tang ,&nbsp;Yuhui Tang ,&nbsp;Xiangsheng Xiao ,&nbsp;Chi Zhang ,&nbsp;Zeyu Shuang ,&nbsp;Xing Li","doi":"10.1016/j.canlet.2025.217734","DOIUrl":"10.1016/j.canlet.2025.217734","url":null,"abstract":"<div><div>Brain metastasis (BM) is a serious complication of increasing incidence in patients with advanced breast cancer, which is characterized by swift deterioration in quality of life with few efficient therapy strategies. There is an urgent clinical requirement to devise potent therapeutic strategies for the prevention and management of brain metastases. Here, we report isoliquiritigenin (ISL), a key bioactive substance extracted from licorice root, which effectively inhibited triple-negative breast cancer (TNBC) brain metastasis (BM) by downregulation of circNAV3. CircRNAs expression analyses and functional studies, coupled with clinical significance investigations identified circNAV3 as a key molecule promoting TNBC BM. Functionally, circNAV3 could promote proliferation, migration, invasion, angiogenesis and capacity to penetrate the blood-brain barrier of TNBC cells. Mechanistically, circNAV3 could competitively bind with miR-4262, hence intercepting the suppressive effect of miR-4262 on ST6GALNAC5. Subsequently, this interplay enhanced EGFR sialylation and activation, initiating the PI3K/Akt pathway and ultimately fostering the development of TNBC brain metastases. In conclusion, our research establishes that ISL impede the initiation and advancement of TNBC brain metastasis by modulation of circNAV3/miR-4262/ST6GALNAC5/EGFR axis, laying a theoretical groundwork for the therapeutic use of ISL in this scenario.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"624 ","pages":"Article 217734"},"PeriodicalIF":9.1,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899868","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":"Microbiome, metabolome, and ionome profiling of cyst fluids reveals heterogeneity in pancreatic cystic neoplasms","authors":"Sen Yang ,&nbsp;Ya Hu ,&nbsp;Ming Cui ,&nbsp;Qiang Xu ,&nbsp;Xianlin Han ,&nbsp;Xiaoyan Chang ,&nbsp;Qingyuan Zheng ,&nbsp;Jinheng Xiao ,&nbsp;Tianqi Chen ,&nbsp;Pengyu Li ,&nbsp;Menghua Dai ,&nbsp;Yupei Zhao","doi":"10.1016/j.canlet.2025.217730","DOIUrl":"10.1016/j.canlet.2025.217730","url":null,"abstract":"<div><div>Pancreatic cystic neoplasms (PCNs) carry variable malignant potential, requiring precise clinical management. However, the heterogeneity and progression of PCNs remain poorly understood. This study analyzed the microbiome, metabolome, and ionome profiles of cyst fluids from 188 patients, including 165 with PCNs and 23 with other cyst types, using PacBio full-length 16S/ITS sequencing, LC-MS/MS, and ICP-MS. Bioinformatic analyses were performed, and metabolic enzyme and endoplasmic reticulum (ER) stress-related gene expression were examined using the PAAD TCGA dataset. PCNs were classified into distinct histopathological subtypes, including mucinous cystic lesions (MCLs) and serous cystic lesions (SCLs). MCLs demonstrated lower microbial diversity compared to SCLs, indicating microbial instability. <em>Streptococcus</em> and <em>Staphylococcus</em> were identified as key taxa in intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs), respectively. MCLs exhibited metabolic shifts towards lipid metabolism, while IPMNs showed distinct metabolic profiles potentially reflecting inflammation-related metabolic reprogramming. Ionic diversity varied among subtypes, with MCLs showing reduced diversity and IPMNs presenting broader ionic profiles. Palmitic acid (PA), a metabolite linked to <em>Streptococcus</em>, may contribute to pro-inflammatory metabolic alterations in IPMN. Our preliminary experiments demonstrated that co-culturing <em>Streptococcus orails (S. orails)</em> with ASAN-PaCa cells promoted their proliferation, accompanied by an elevation of PA levels in the supernatant. This integrative microbiome–metabolome–ionome analysis highlights histopathological heterogeneity among PCNs. While mechanistic associations remain to be fully defined, mucinous lesions may be more susceptible to microbe-driven metabolic disruption, with <em>Streptococcus</em>-associated lipid alterations as a potential contributing factor.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"623 ","pages":"Article 217730"},"PeriodicalIF":9.1,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of SPHK1 fuels inflammation to drive KRAS-mutated lung adenocarcinoma","authors":"Andreea C. Luca ,&nbsp;Margarita Kurnaeva ,&nbsp;Daniel K. John ,&nbsp;Michael Machtinger ,&nbsp;Nadja H.J. Vollmer ,&nbsp;Bernadette Mödl ,&nbsp;J. Thomas Hannich ,&nbsp;Margret Eckhard ,&nbsp;Hon S. Lam ,&nbsp;Laszlo Musiejovsky ,&nbsp;Christoph Trenk ,&nbsp;Monika Homolya ,&nbsp;Clemens Fürnsinn ,&nbsp;Andy Sombke ,&nbsp;Gernot Schabbauer ,&nbsp;Robert Eferl ,&nbsp;Omar Sharif ,&nbsp;Emilio Casanova ,&nbsp;Herwig P. Moll","doi":"10.1016/j.canlet.2025.217733","DOIUrl":"10.1016/j.canlet.2025.217733","url":null,"abstract":"<div><div>Inflammation is a widely recognized key contributor to KRAS-driven lung adenocarcinoma (LUAD). Tumor-associated macrophages (TAM) are an integral part of the tumor microenvironment and create a supportive niche that sustains inflammation-driven tumorigenesis. In the present study, we unravel a dual role of sphingosine kinase 1 (SPHK1) in KRAS-driven LUAD. While SPHK1 promotes tumorigenesis in in vitro experimental models, it paradoxically suppresses tumorigenesis in in vivo models of KRAS-mutated LUAD. Mechanistically, tumor-intrinsic loss of SPHK1 leads to disrupted lipid homeostasis, increased inflammation and infiltration by TAM, ultimately driving tumor progression. Thus, our study suggests that clinically targeting the SPHK1/S1P axis could potentially result in increased tumor progression, possibly by rewiring the tumor microenvironment toward a more inflammatory and pro-tumorigenic state.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"623 ","pages":"Article 217733"},"PeriodicalIF":9.1,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143858983","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":"COL1A1-positive endothelial cells promote gastric cancer progression via the ANGPTL4-SDC4 axis driven by endothelial-to-mesenchymal transition","authors":"Quanzhong Liu ,&nbsp;Miao Yu ,&nbsp;Zihan Lin ,&nbsp;Lingxiang Wu ,&nbsp;Peng Xia ,&nbsp;Mengyan Zhu ,&nbsp;Bin Huang ,&nbsp;Wei Wu ,&nbsp;Ruohan Zhang ,&nbsp;Kening Li ,&nbsp;Lingjun Zhu ,&nbsp;Qianghu Wang","doi":"10.1016/j.canlet.2025.217731","DOIUrl":"10.1016/j.canlet.2025.217731","url":null,"abstract":"<div><div>Gastric cancer (GC) is an aggressive and heterogeneous disease with poor survival outcomes. The progression of GC involves complex, multi-step processes. Endothelial cells (ECs) play a crucial role in tumor angiogenesis, proliferation, invasion, and metastasis, particularly through the process of endothelial-to-mesenchymal transition (EndoMT). However, the specific role and mechanisms of EndoMT in gastric cancer remain unclear. Based on 6 GC single-cell RNA-sequencing (scRNA-seq) cohorts (samples = 97), we established an EndoMT-related gene signature, termed EdMTS. Leveraging this gene signature, ssGSEA was applied to calculate sample scores across multiple bulk RNA-seq datasets, which include information on immunotherapy, metastasis, GC progression, and survival. Moreover, we applied the Monocle2 method to calculate cell pseudotime and used CellChat to analyze interactions between malignant and EC cells. We verified the molecular mechanism by multiple immunofluorescence and cell function experiments. Findings In this study, we established a single-cell atlas of ECs in GC and identified a subpopulation of <em>COL1A1</em>⁺ ECs that play a critical role in tumor progression and metastasis. These <em>COL1A1</em>⁺ ECs were significantly associated with worse clinical outcomes in GC patients. Further analysis revealed that <em>COL1A1</em>⁺ ECs originated from lymphatic ECs and underwent EndoMT through the upregulation of CEBPB, driving tumor invasiveness. Moreover, <em>COL1A1</em>⁺ ECs interacted with malignant cells via ANGPTL4-SDC4 axis, enhancing invasion and migration. These findings provide a deeper understanding of the role of <em>COL1A1</em>⁺ ECs in GC progression and highlight potential therapeutic targets for disrupting the EndoMT process in these cells to provide a benefit for GC patients.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"623 ","pages":"Article 217731"},"PeriodicalIF":9.1,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855862","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}