Molecular Cancer Research最新文献

{"title":"Mapping the FOXA1 Interactome in ER+ Breast Cancer Cells Using Proximity Labeling Reveals Novel Interactions with the Orphan Nuclear Receptor NR2C2.","authors":"Rosemary N Plagens, Carla S Rodriguez Tirado, Shen Li, Natalia Maldonado-Vazquez, Ingrid M Montes-Rodriguez, Julie Dutil, Christine A Mills, Laura E Herring, Hector L Franco","doi":"10.1158/1541-7786.MCR-25-0085","DOIUrl":"10.1158/1541-7786.MCR-25-0085","url":null,"abstract":"<p><p>FOXA1 is a pioneer transcription factor essential for chromatin accessibility and transcriptional regulation in hormone-driven cancers. In breast cancer, FOXA1 plays a central role in facilitating nuclear receptor binding, reprogramming enhancer landscapes, and promoting transcriptional changes associated with therapy resistance. Whereas FOXA1's function has been primarily studied in the context of estrogen receptor-α (ER), its broader protein interaction network remains incompletely defined. In this study, we systematically map FOXA1-interacting proteins in ER-positive breast cancer cells using proximity-dependent biotin labeling (miniTurbo) combined with quantitative LC-MS/MS proteomics. We engineered MCF-7 cell lines stably expressing miniTurbo-tagged FOXA1 at either the N-terminus or C-terminus to ensure comprehensive coverage of interaction interfaces. This approach recovered known FOXA1 partners, including AR, MLL3, YAP1, and GATA3, and identified 157 previously unreported FOXA1 interactors. Notably, 42 of these novel partners, including NR2C2, were significantly associated with poor relapse-free survival in patients with ER-positive breast cancer. To demonstrate the utility of this resource, we characterized the FOXA1-NR2C2 interaction in depth. Integrating chromatin immunoprecipitation sequencing and RNA sequencing, we show that FOXA1 and NR2C2 co-occupy a subset of genomic regions and drive co-regulated transcriptional programs involved in tumor progression. Our study reveals an expanded FOXA1 interactome and new insights into its functional network in breast cancer, providing candidate proteins for further exploration as biomarkers or therapeutic targets.</p><p><strong>Implications: </strong>These findings expand the FOXA1 interactome in breast cancer and uncover new candidate proteins with potential as biomarkers and therapeutic targets in hormone-driven tumors.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"997-1011"},"PeriodicalIF":5.8,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DDR2 Confers Ferroptosis Resistance to Cancer-Associated Fibroblasts and Attenuates PARPi Sensitivity of Ovarian Tumor Cells.","authors":"Julien Lesage, Alessandra DiMauro, Angela M Schab, Seth Stidham, Mary M Mullen, Katherine C Fuh, Gregory D Longmore","doi":"10.1158/1541-7786.MCR-25-0268","DOIUrl":"10.1158/1541-7786.MCR-25-0268","url":null,"abstract":"<p><p>In ovarian cancer, resistance to conventional treatments has prompted the search for alternative targets and/or cells within the tumor microenvironment that could enhance tumor cell death. Ferroptosis, an iron-dependent, lipid peroxide-triggered form of cell death, is one such pathway. Cancer-associated fibroblasts (CAF) are key stromal cells in the ovarian tumor microenvironment that can affect therapeutic responses. Using various genetic approaches, we generated multiple DDR2-expressing and DDR2-deficient human ovarian tumor and mouse breast tumor CAFs. We found that DDR2 expression in CAFs protects these cells from ferroptosis by regulating the xCT-GSH-GPX4 antioxidant pathway and cellular iron metabolism. Specifically, DDR2 regulates xCT expression through noncanonical p62-dependent NRF2 activation and the labile iron pool by controlling ferritinophagy. CAFs secrete factors, in a DDR2-dependent manner, that provide protection to ovarian tumor cells against olaparib-induced cell death, a clinically relevant PARP inhibitor (PARPi). Finally, we found that high expression of DDR2 in the stromal cells of human ovarian tumors is associated with poor response to PARPi in clinical trials. These findings suggest that ferroptotic regulation by DDR2 in ovarian tumor CAFs could affect therapeutic sensitivity and resistance to PARPi.</p><p><strong>Implications: </strong>The action of the collagen receptor tyrosine kinase DDR2 in CAFs confers PARPi protection to ovarian tumor cells by protecting CAFs from ferroptosis.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"1012-1024"},"PeriodicalIF":4.7,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12700032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fucosylated N-Glycan Landscape of Triple-Negative Breast Cancer.","authors":"Danielle A Scott, Souvik Seal, Laura Spruill, Jaclyn Dunne, Graham Colditz, Anand S Mehta, Richard R Drake, Marvella E Ford, Peggi M Angel","doi":"10.1158/1541-7786.MCR-25-0483","DOIUrl":"10.1158/1541-7786.MCR-25-0483","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer lacking targeted therapies. Although aberrant N-glycosylation is a hallmark of malignancy, the specific roles of core-fucosylated (CF) and outer arm-fucosylated (OAF) N-glycans in TNBC progression and patient survival remain underexplored. This study utilized multiplexed glycomics by matrix-assisted laser desorption/ionization imaging mass spectrometry to spatially profile 348 N-glycans in 59 TNBC tumors with clinical characteristics including survival data. Spatial analysis revealed distinct localization patterns of CF and OAF isomers within tumor microenvironments. Strikingly, OAF glycans, but not CF, were strongly associated with tumor stage, with expression increasing from stage I to III and then declining in stage IV. Furthermore, 68 N-glycans were significantly associated with survival outcomes; 36 (52%) of these were OAF-modified, including polylactosamine structures previously linked to metastasis in breast cancer. High expression of OAF polylactosamines correlated with poor prognosis and was detectable in early-stage TNBC tumors, underscoring their potential as prognostic biomarkers.</p><p><strong>Implications: </strong>These findings demonstrate that OAF N-glycans are dynamic, structure-specific markers of TNBC progression and survival, and their early detection and strong prognostic value highlight potential utility in patient stratification and personalized therapy.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"984-996"},"PeriodicalIF":4.7,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12670077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer Genomic Alterations and Microenvironmental Features Encode Synergistic Interactions with Disease Outcomes.","authors":"Masroor Bayati, Zoe P Klein, Alexander T Bahcheli, Mykhaylo Slobodyanyuk, Jeffrey To, Kevin C L Cheng, Jigyansa Mishra, Diogo Pellegrina, Kissy Guevara-Hoyer, Chris McIntosh, Mamatha Bhat, Jüri Reimand","doi":"10.1158/1541-7786.MCR-25-0475","DOIUrl":"10.1158/1541-7786.MCR-25-0475","url":null,"abstract":"<p><p>Oncogenesis, tumor progression, and therapy response are shaped by somatic alterations in the cancer genome and features of the tumor-immune microenvironment (TME). How interactions between these two systems influence tumor evolution and clinical outcomes remains incompletely understood. To address this challenge, we developed the multi-omics analysis framework PACIFIC that systematically integrates genetic cancer drivers and infiltration profiles of immune cells to find pairwise combinations of drivers and TME characteristics that jointly associate with clinical outcomes. By analyzing 8,500 primary tumor samples of 26 cancer types, we report 34 immunogenomic interactions (IGX) in 13 cancer types in which context-specific combinations of genomic alterations and immune cell levels were significantly correlated with patient survival. Subsets of tumor samples defined by some IGXs were characterized by tumor-intrinsic and microenvironmental metrics of immunogenicity and differential expression of immunotherapy target genes. In luminal-A breast cancer, an IGX involving MEN1 deletion combined with reduced levels of neutrophils associated with lower progression-free survival and deregulation of immune signaling pathways, as observed in two independent cancer genomics datasets. These results showcase the ability of PACIFIC to integrate complex multi-omics datasets with clinical information, enabling the identification of clinically relevant IGXs. Such interactions provide a rich set of hypotheses for mechanistic studies and the development of biomarkers and therapeutic targets.</p><p><strong>Implications: </strong>Co-occurrence patterns of cancer drivers and TME characteristics highlight synergistic interactions with prognostic potential.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"971-983"},"PeriodicalIF":4.7,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12670080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor Cholesterol Synthesis, Statin Use, and Lethal Prostate Cancer.","authors":"Sinead Flanagan, Rosina T Lis, Ying Huang, Lina Jehane, Jane B Vaselkiv, Emma H Allott, Stephen P Finn, Tamara L Lotan, Michelangelo Fiorentino, Massimo Loda, Gwo-Shu Mary Lee, Goutam Chakraborty, Philip W Kantoff, Lorelei A Mucci, Konrad H Stopsack","doi":"10.1158/1541-7786.MCR-24-0864","DOIUrl":"10.1158/1541-7786.MCR-24-0864","url":null,"abstract":"<p><p>Prostate tumor cells produce cholesterol de novo, and statin therapy targets the initial rate-limiting enzyme in this process, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR). The extent to which the expression of HMGCR in prostate tumors could influence progression and predict the potential antineoplastic effects of statins remains unclear. In a prospective cohort study of 1,098 men diagnosed with primary prostate cancer from 1982 to 2009 in the Health Professionals Follow-up Study and Physicians' Health Study, 16% of prostate tumors showed strong HMGCR staining intensity, and 31% showed no staining. HMGCR expression was higher in tumors with PTEN loss but did not differ by statin use or long-term dietary cholesterol or saturated fat intake. Participants were followed for lethal events (distant metastases or prostate cancer-related death) over up to 32 years, and 96 lethal events occurred in those without metastases at diagnosis. Strong HMGCR expression was associated with higher rates of lethal prostate cancer (HR, 2.2; 95% confidence interval, 1.3-3.7), adjusting for age at diagnosis and Gleason score but without a linear dose response. In vitro, in the LNCaP human prostate cancer cell line, atorvastatin affected tumor cell viability in cells with experimentally lowered HMGCR expression. This study corroborates that high cholesterol synthesis in prostate tumor cells is associated with PTEN loss, aggressive tumor characteristics, and a greater risk of lethality.</p><p><strong>Implications: </strong>High expression of HMGCR, the first rate-limiting enzyme of cholesterol synthesis, is a feature of prostate tumors that are more likely to progress to metastatic disease or death from prostate cancer.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"1025-1033"},"PeriodicalIF":5.8,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12434729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"β-Catenin-Cohesin Ring-CEGRs/ALCDs Axis Activation Contributes to the Development of Hepatoblastoma and Fibrolamellar HCC.","authors":"Yasmeen Fleifil, Ruhi Gulati, Katherine Jennings, Ina Kycia, Alex Bondoc, Gregory Tiao, James Geller, Matthew Weirauch, Khashayar Vakili, Lubov Timchenko, Nikolai Timchenko","doi":"10.1158/1541-7786.MCR-25-0236","DOIUrl":"10.1158/1541-7786.MCR-25-0236","url":null,"abstract":"<p><p>The pediatric and adolescent liver cancers, hepatoblastoma (HBL) and fibrolamellar hepatocellular carcinoma (FLC), respectively, are dangerous diseases requiring aggressive surgery, when feasible, and nontargeted toxic chemotherapy for a chance of cure due to insufficient knowledge of underlying molecular mechanisms. We have previously reported the essential role of ph-S675-β-catenin in the reorganization of genomic structure in HBL and FLC by oncogenic activation via chromosomal regions called cancer-enhancing genomic regions or aggressive liver cancer domains (CEGR/ALCD). In FLC, the fusion DNAJB1-PKAc (J-PKAc) oncoprotein phosphorylates β-catenin at Ser675, triggering such CEGRs/ALCDs-mediated activation of oncogenes. In this study, we found that all members of the cohesin ring-CTCF, Rad21, SMC1, SMC3, and STAG1-and β-catenin-TCF4 are bound to CEGRs/ALCDs of oncogenes in HBL and FLC, as well as many other cancers, and that this binding increases transcription. Examination of a large cohort of HBL and FLC samples revealed that cohesin ring expression is dramatically elevated in the majority. The cohesin ring, as well as the ph-S675-β-catenin-TCF4-p300 complex, is detected on both the promoter and intron-located CEGRs/ALCDs of NRF2 and Thy1, correlating with increased transcription. This suggests that the cohesin ring creates the DNA loop for oncogene activation. The inhibition of the cohesin ring by JQ1 reduces the proliferation of HBL and FLC cells in culture, as well as cells expressing the FLC-specific J-PKAc fusion oncogene.</p><p><strong>Implications: </strong>These studies provide evidence that J-PKAc-β-catenin and the cohesin ring cooperate in oncogenic activation for both HBL and FLC.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"901-912"},"PeriodicalIF":5.8,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12969850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic Signatures of Poor Prognosis in Merkel Cell Carcinoma: A Single-Institution Prospective Study.","authors":"Joshua D Smith, Apurva D Bhangale, Wenjin Gu, Collin Brummel, Elizabeth Gensterblum-Miller, Scott McLean, Paul W Harms, Kelly L Harms, Christopher K Bichakjian, Matthew E Spector, Ryan E Mills, J Chad Brenner","doi":"10.1158/1541-7786.MCR-24-1138","DOIUrl":"10.1158/1541-7786.MCR-24-1138","url":null,"abstract":"<p><p>Merkel cell carcinoma (MCC) is an aggressive disease with poor survival outcomes and increasing incidence. There is a clear and present need for enhanced understanding of cellular mechanisms of tumorigenesis, validation of robust genetic signatures predictive of aggressive disease, and novel informatics tools to simplify analysis of Merkel cell polyomavirus (MCPyV)-host genome interactions. Genomic DNA was harvested from 54 MCC tumors for exome sequencing and in-depth genetic profiling of a 226-gene panel. We further developed a robust informatics package (MCPyViewer) optimized for MCPyV integration site analysis with graphical output to simplify usability for end users. Finally, we assessed the prognostic impact of specific genetic signatures on MCC-specific survival in our cohort. Our study included 54 patients (n = 44 MCPyV positive), 11 (20.4%) of whom had died of MCC at last follow-up. Human genes altered at high frequency included LRP1B (n = 10, 18.5%), FAT1 (n = 9, 16.7%), KMT2D (n = 9, 16.7%), and RB1 (n = 7, 13.0%). In 36 of 44 (81.8%) MCPyV-positive tumors, we identified viral integration into the human genome with a median of two events per tumor. In six tumors, MCPyV integrated into Catalogue of Somatic Mutations in Cancer tier 1 or tier 2 cancer-related human genes.</p><p><strong>Implications: </strong>A combined genomics score incorporating tumor mutational burden and copy-number variation was strongly prognostic of MCC-specific survival controlling for lymph node metastases and tumor MCPyV status; thus, our study adds critical understanding to prognostic markers and tumorigenic mechanisms in MCC.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"923-935"},"PeriodicalIF":4.7,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12336863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential Control of Growth and Identity by HNF4α Isoforms in Pancreatic Ductal Adenocarcinoma.","authors":"Pengshu Fang, Emily R Wilson, Sydney N Larsen, Walter A Orellana, Margaret A Hall, Chris Stubben, Acramul Haque Kabir, Kajsa Affolter, Richard A Moffitt, Xiaoyang Zhang, Eric L Snyder","doi":"10.1158/1541-7786.MCR-25-0175","DOIUrl":"10.1158/1541-7786.MCR-25-0175","url":null,"abstract":"<p><p>Although transcriptomic studies have stratified pancreatic ductal adenocarcinoma (PDAC) into clinically relevant subtypes, classic or basal-like, further research is needed to identify the transcriptional regulators of each subtype. Previous studies identified HNF4α as a key regulator of the classic subtype. Still, the distinct contributions of its isoforms (P1 and P2), which display dichotomous functions in normal development and gastrointestinal malignancies, remain unexplored. In this study, we show that HNF4α-positive human PDAC tumors exhibit uniform expression of P2 isoforms but variable expression of P1 isoforms. To dissect the roles of each isoform in PDAC, we performed functional, transcriptomic, and epigenetic analyses after exogenous expression in HNF4α-negative models or CRISPRi-mediated knockdown of endogenous isoforms. We demonstrated that P1 isoforms are less compatible with growth and stronger transcriptional regulators than P2. Despite both isoforms sharing a common DNA-binding domain, P1 isoforms displayed stronger binding at HNF4α target genes, resulting in increased transcriptional activity. These findings provide a detailed characterization of HNF4α P1 and P2 isoforms and their distinct roles in PDAC biology.</p><p><strong>Implications: </strong>HNF4α isoforms exhibit heterogeneous expression in PDAC and have distinct effects on proliferation and gene expression, including markers of clinically relevant molecular subtypes.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"936-952"},"PeriodicalIF":4.7,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12333154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The LINC00519/hsa-miR-22-3p/MECOM Axis Accelerates Intrahepatic Cholangiocarcinoma Progression through PI3K/AKT Signaling.","authors":"Zhuxin Gu, Yanjun Sun, Fajing Chen, Weiwei Gu, Xiaohua Lu, Suming Zhao, Qinan Geng, Yang Yang","doi":"10.1158/1541-7786.MCR-25-0207","DOIUrl":"10.1158/1541-7786.MCR-25-0207","url":null,"abstract":"<p><p>Intrahepatic cholangiocarcinoma (ICC) is the second most common liver cancer. LINC00519 plays a prominent role in the progression of numerous cancers. To explore the molecular mechanism of LINC00519 in ICC, the expressions of LINC00519, hsa-miR-22-3p, and MECOM in ICC were assessed using the ENCORI database and qRT-PCR. The biological functions of LINC00519 in ICC were examined using a clone formation experiment, Transwell analysis, flow cytometry, and Western blot. Meanwhile, the mechanism of LINC00519 in ICC was determined by a dual-luciferase reporter assay. Results showed that LINC00519 and MECOM were highly expressed in ICC, whereas hsa-miR-22-3p was decreased. Functionally, silencing LINC00519 weakened ICC cell proliferation and migration and induced cell apoptosis. Also, LINC00519 knockdown repressed the PI3K/AKT (protein kinase B) pathway. Mechanistically, LINC00519 acted as a competitive endogenous RNA to target MECOM by sponging hsa-miR-22-3p. Meanwhile, rescue assays further proved that low LINC00519 expression restrained ICC cell proliferation and migration and accelerated apoptosis through the PI3K/AKT pathway by miR-22-3p/MECOM. In conclusion, this research revealed a novel LINC00519/hsa-miR-22-3p/MECOM regulatory axis and PI3K/AKT pathway that modulated ICC progression.</p><p><strong>Implications: </strong>This study deepens the understanding of the noncoding RNA regulatory network in ICC and provides potential targets for the diagnosis and targeted therapy of ICC.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"913-922"},"PeriodicalIF":4.7,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12580760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MACC1-AS1: An Emerging Star in the Field of Tumor Biology with Bright Futures in Medicine.","authors":"Li Dong, Weidong Li, Wei Zhu, Yamin Sun","doi":"10.1158/1541-7786.MCR-25-0170","DOIUrl":"10.1158/1541-7786.MCR-25-0170","url":null,"abstract":"<p><p>Long noncoding RNAs act as modulators, with significant influence on a wide array of biological functions. They form an extensive communication network between genes and contribute to the pathophysiology of various human diseases, especially cancer. A growing body of research has demonstrated that long noncoding RNAs, acting either as promoters or inhibitors of oncogenesis, are intricately linked to the initiation and progression of cancer. Metastasis-associated colon cancer 1 antisense RNA1 (MACC1-AS1) is a newly identified long noncoding RNA that is abnormally expressed in various types of human tumors. Poor clinical characteristics, such as larger tumor size, advanced tumor stage, lymph node metastasis, and a lower overall survival rate, are linked to the overexpression of MACC1-AS1. MACC1-AS1 exerts a complex regulatory function: It acts as a competitive RNA, interacts with multiple proteins, and influences diverse pathways, leading to tumor development. It is essential to note the decreased efficacy of conventional chemotherapy drugs, which diminishes the efficacy of cancer treatment. Ongoing research has been highlighting the multifaceted functions of MACC1-AS1, and thus, it is required to unravel its exact molecular mechanisms. In this overarching review, we explore the significance of MACC1-AS1 as a potential cancer treatment target and biomarker. This study can potentially play an important role in the advancement of the field and confirm its potential clinical applicability.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"895-900"},"PeriodicalIF":4.7,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}