Molecular Carcinogenesis最新文献

{"title":"miR-135b-5p/PDE3B Axis Regulates Gemcitabine Resistance in Pancreatic Cancer Through Epithelial-Mesenchymal Transition.","authors":"Yuxuan Fu, Liangsheng Chen, Neng Lv, Jia Wang, Shuwei Yu, Qilu Fang, Wenxiu Xin","doi":"10.1002/mc.23914","DOIUrl":"https://doi.org/10.1002/mc.23914","url":null,"abstract":"<p><p>Gemcitabine-based chemotherapy is an effective treatment for pancreatic cancer (PC), but gemcitabine resistance frequently compromises the therapeutic efficacy, resulting in clinical chemotherapeutic failure and a poor prognosis for patients. In this study, we investigated the mechanisms of gemcitabine chemoresistance in PC by examining the roles of microRNAs linked to gemcitabine resistance and their downstream signaling pathways. In vitro experiments were performed to alter miR-135b-5p levels in PC parental and drug-resistant cells to probe its function. miR-135b-5p targets PDE3B was confirmed by using RNA-seq technology to screen for gemcitabine-resistance-associated mRNAs in PC. A series of rescue experiments were performed after cotransfection, demonstrating that PDE3B could reverse miR-135b-5p-mediated chemoresistance and epithelial-mesenchymal transition (EMT). These findings indicate that the miR-135b-5p/PDE3B axis generates resistance by stimulating the EMT signaling pathway, which provides new insights into gemcitabine chemoresistance in PC.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764514","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}

{"title":"Computed Tomography-Based Radiomics and Genomics Analyses for Survival Prediction of Stage III Unresectable Non-Small Cell Lung Cancer Treated With Definitive Chemoradiotherapy and Immunotherapy.","authors":"Yuxin Geng, Tianwen Yin, Yikun Li, Kaixing He, Bingwen Zou, Jinming Yu, Xiao Sun, Tao Zhang, Feifei Teng","doi":"10.1002/mc.23883","DOIUrl":"10.1002/mc.23883","url":null,"abstract":"<p><p>The standard therapy for locally unresectable advanced non-small cell lung cancer (NSCLC) is comprised of chemoradiotherapy (CRT) before immunotherapy (IO) consolidation. However, how to predict treatment outcomes and recognize patients that will benefit from IO remain unclear. This study aimed to identify prognostic biomarkers by integrating computed tomography (CT)-based radiomics and genomics. Specifically, our research involved 165 patients suffering from unresectable Stage III NSCLC. Cohort 1 (IO following CRT) was divided into D1 (n = 74), D2 (n = 32), and D3 (n = 26) sets, and the remaining 33 patients treated with CRT alone were grouped in D4. According to the CT images of primary tumor regions, radiomic features were analyzed through the least absolute shrinkage and selection operator (LASSO) regression. The Rad-score was figured out to forecast the progression-free survival (PFS). According to the Rad-score, patients were divided into high and low risk groups. Next-generation sequencing was implemented on peripheral blood and tumor tissue samples in the D3 and D4 cohorts. The maximum somatic allele frequency (MSAF) about circulating tumor DNA levels was assessed. Mismatch repair and switching/sucrose non-fermenting signaling pathways were significantly enriched in the low-risk group compared to the high-risk group (p < 0.05). Moreover, patients with MSAF ≥ 1% and those showing a decrease in MSAF after treatment significantly benefited from IO. This study developed a radiomics model predicting PFS after CRT and IO in Stage III NSCLC and constructed a radio-genomic map to identify underlying biomarkers, supplying valuable insights for cancer biology.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"733-743"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008764","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":"Glutamine, Serine and Glycine at Increasing Concentrations Regulate Cisplatin Sensitivity in Gastric Cancer by Posttranslational Modifications of KDM4A.","authors":"Junhao Fu, Yuqi Ni, Yuqing Hu, Wanfen Tang, Jianfei Fu, Yue Wang, Shian Yu, Wenxia Xu","doi":"10.1002/mc.23881","DOIUrl":"10.1002/mc.23881","url":null,"abstract":"<p><p>Gastric cancer is a common digestive system tumor with a high resistance rate that reduces the sensitivity to chemotherapy. Nutrition therapy is an important adjuvant approach to favor the prognosis of gastric cancer. Dietary amino acids contribute greatly to gastric cancer progression by mediating tumor gene expressions, epigenetics, signal transduction, and metabolic remodeling. In the present study, 20 types of amino acids were screened and glutamine, glycine and serine were identified as the critical regulators of cisplatin (DDP) sensitivity in gastric cancer cells. Moreover, KDM4A acetylation drove the reduced chemotherapy sensitivity in gastric cancer cells by maintaining protein stability and activating DNA repair ability when the concentrations of glutamine (Gln), serine (Ser), and glycine (Gly) decreased. Conversely, Gln/Ser/Gly at increasing concentrations stimulated ubiquitination degradation of KDM4A, which in turn elevated the sensitivity of gastric cancer cells to chemotherapy. Our findings unveiled the role of amino acid nutrition in regulating chemotherapy sensitivity of gastric cancer and the underlying mechanism, thus providing a scientific basis for expanding the clinical significance of nutrition therapy for gastric cancer patients.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"703-715"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008765","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}

{"title":"Hypoxia Promotes Malignant Progression of Colorectal Cancer by Inducing POSTN⁺ Cancer-Associated Fibroblast Formation.","authors":"Jian Qin, Shangshang Hu, Yuhan Chen, Mu Xu, Qianni Xiao, Jinwei Lou, Muzi Ding, Huiling Sun, Tao Xu, Yuqin Pan, Shukui Wang","doi":"10.1002/mc.23882","DOIUrl":"10.1002/mc.23882","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is one of the most common malignancies. Hypoxia can promote the occurrence and development of CRC. However, how hypoxia regulates the CRC immune microenvironment needs to be further explored. The bulk RNA sequencing data and clinicopathological information of CRC patients were enrolled from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The single-cell RNA sequencing (scRNA-seq) datasets of CRC were collected from and analyzed from the GEO database and the ArrayExpress database. The score of the hypoxia gene set was estimated using the \"ssGSEA\" algorithm in the \"GSVA\" R package. The functional characteristics of CAF subtypes were studied by bioinformatics analysis and in vitro experiments, and a prognostic model was constructed based on machine learning correlation. Hypoxia is associated with poor prognosis in CRC patients. Periostin (POSTN) + Fib is a cancer-associated fibroblast (CAF) closely associated with hypoxia, and high infiltration of POSTN + Fib is associated with adverse outcomes in overall survival (OS) and relapse-free survival (RFS) in CRC patients. Hypoxia can induce POSTN expression and secretion in CAFs. Hypoxia-induced increase of POSTN expression in CAFs can significantly promote the migration and proliferation of CRC cells. Hypoxia-induced increase of POSTN expression in CAFs can significantly promote the proliferation and migration of CRC cells. The POSTN⁺Fib Hypoxia-Related Risk Model (PFHRM) can predict the survival and immunotherapy response of CRC patients. Our study identified a POSTN⁺Fib cell subpopulation closely associated with hypoxia, which promotes the malignant progression of CRC. The development of PFHRM provides a theoretical basis for improving patient survival and prognosis.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"716-732"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008766","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}

{"title":"PTPN2 Expression in Hypopharyngeal Squamous Cell Carcinoma and Its Clinical Significance.","authors":"Xue Li, Hua Feng, Hengheng Jian, Shilan Zhang, Zhaoli Liao Tai, Xiaoyu Wang, Fengzhi Lu, Zuwei Liu, Tingchao Li, Yangsong Ji, Youxuan Liu, Zuxia Ma","doi":"10.1002/mc.23872","DOIUrl":"10.1002/mc.23872","url":null,"abstract":"<p><p>This study aimed to explore PTPN2 expression levels in Hypopharyngeal Squamous Cell Carcinoma (HPSCC) tissues and their relationship with the clinical characteristics and prognosis of HPSCC patients. PTPN2, a protein tyrosine phosphatase, has recently emerged as a promising target for cancer immunotherapy, and in many previous studies, PTPN2 may have a significant role in the growth, differentiation, metabolism and immune response of head and neck malignant tumors. In this study, PTPN2 expression in Head and Neck Squamous Cell Carcinoma (HNSCC) and other cancer tissues was analyzed using datasets derived from the Sangerbox database. Furthermore, we analyzed data on PTPN2 mRNA levels across various clinical stages of HNSCC (I, II, III, and IV), which was extracted from the Gene Expression Profiling Interactive Analysis (GEPIA) database. Clinical data from patients who underwent surgical resection for hypopharyngeal malignancies at the Third Affiliated Hospital of Zunyi Medical University between January 2013 and January 2024 were also obtained and analyzed. The patient specimens were categorized into two groups (the HPSCC tumor and paracarcinoma tissue groups) and compared for PTPN2 expression using Immunohistochemistry (IHC), Immunofluorescence (IF), and Western Blot (WB) analyses. According to the results, HPSCC patients were mostly elderly males with a history of tobacco and alcohol abuse. Furthermore, the most common site of HPSCC onset was piriform sinuses, and the disease was often diagnosed in the middle or advanced stages. Additionally, HPSCC tissues exhibited PTPN2 upregulation. Moreover, PTPN2 expression did not correlate significantly with patients' gender, Smoking Index (SI), alcohol abuse, tumor diameter, Hypertension (HTN), diabetes, and M stage. On the other hand, it correlated with HPSCC patients' T-stage, N-stage, Overall Survival (OS), and clinical stage. Based on these findings, we deduced that high PTPN2 expression could be involved in HPSCC patients' poor prognosis.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"629-637"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952057","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}

{"title":"Adipose Secreted Slit2-C Suppresses Breast Cancer Invasion Through cAMP/PKA Transition.","authors":"Haolin Hu, Kexuan Li, Lifei Han, Yangyang Gu, Zhenling Ji","doi":"10.1002/mc.23915","DOIUrl":"https://doi.org/10.1002/mc.23915","url":null,"abstract":"<p><p>Adipose tissue activation plays a positive role in breast cancer outcomes, consistent with the improved outcomes observed through exercise and weight loss mediated by brown and beige fat. However, the underlying mechanism of this process remains unclear. C-terminal fragment of Slit2 (Slit2-C), endogenously produced by brown or beige adipose cells could increase the thermogenic process of adipose cells in autocrine and paracrine manners. Here, we show that Slit2-C dominantly reduces breast cancer cell invasion through cAMP/PKA mediated inhibition of epithelial-mesenchymal transition. In the process, Slit2-C plays a vital role as a positive regulator of cAMP/PKA signaling in breast cancer. As a result, the overexpression of Slit2-C leads to a reduction in cancer cell invasion and an increase in both the epithelial phenotype and thermogenesis. Besides, inhibiting PKA phosphorylation with H89 reversed the reduced invasion process seen in human breast cancer cells overexpressing Slit2-C, which suggests that the effect of Slit2-C on reducing invasion is mediated through the activation of PKA signaling. Taken together, our study suggests that the modulation of the Slit2-C/cAMP/PKA axis might be a potential targeting therapeutic intervention in aggressive breast cancers.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764490","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}

{"title":"KCNE3 Facilitates M1 Macrophage Polarization by Suppressing the Wnt/β-Catenin Pathway, Inhibiting Glioma Proliferation, Migration, and Invasion.","authors":"Shangyu Liu, Qiao Li, Liang Niu, Peng Feng, Wenshan Li, Ying Dang, Juan Jia, Guoqiang Yuan, Yawen Pan","doi":"10.1002/mc.23911","DOIUrl":"https://doi.org/10.1002/mc.23911","url":null,"abstract":"<p><p>The glioma microenvironment is critical for tumor growth, where reprogramming M2-polarized tumor-associated macrophages/microglia (TAMs) to an antitumor M1 phenotype represents a promising therapeutic strategy. While the potassium channel regulatory subunit KCNE3 has been implicated in tumorigenesis across malignancies, its functional role in shaping the glioma microenvironment remains undefined. Here, we leveraged transcriptome data from the Gene Expression Omnibus (GEO) to identify KCNE3 as a TAM-enriched gene in gliomas. To interrogate its mechanistic contributions, we generated KCNE3-knockdown and overexpressing macrophages and evaluated their impact on glioma cells in coculture systems. Silencing KCNE3 in macrophages significantly attenuated glioma cell proliferation, migration, and invasion in vitro, accompanied by enhanced M1 polarization. Mechanistically, KCNE3 depletion suppressed Wnt/β-catenin signaling, driving increased secretion of pro-inflammatory cytokines TNF-α, IL-6, and IL-12. Conversely, KCNE3 overexpression reversed these effects, promoting M2-like characteristics and tumor-supportive behaviors. These findings establish KCNE3 as a key modulator of TAM phenotype and glioma progression, suggesting that targeted KCNE3 inhibition may disarm pro-tumorigenic immune responses to improve therapeutic outcomes. This study uncovers a novel actionable method in glioma immunotherapy.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730919","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}

{"title":"TSPAN31 Activates Fatty Acid Metabolism and PI3K/AKT Pathway to Promote Tumor Progression in Breast Cancer.","authors":"Wenquan Luo, Yuxiang Sun, Liang Cao","doi":"10.1002/mc.23912","DOIUrl":"https://doi.org/10.1002/mc.23912","url":null,"abstract":"<p><p>Breast cancer (BC) is one of the most common human malignancies, but the mechanisms of BC have not been fully elucidated. Recently, tetraspanin 31 (TSPAN31) is reported to be linked to cancer progression. However, the function of TSPAN31 remains unclear in BC. Investigation of the function and potential mechanism of TSPAN31 in BC was the purpose of this study. Immunohistochemistry, western blot, and quantitative real-time polymerase chain reaction were applied to measure TSPAN31 expression. Loss and gain functional experiments were utilized to survey the influences of TSPAN31 on BC biological process, including cell growth, invasion, migration, and fatty acid metabolism. Mechanistically, Kyoto Encyclopedia of Genes and Genomes analysis based on DepMap database and Gene Set Enrichment Analysis based on The Cancer Genome Atlas database were executed to find TSPAN31-related pathway. Western blot was carried out to assess the changes of fatty acid synthase (FASN), sterol regulatory element binding protein 1 (SREBP1), acyl-CoA synthetase long-chain family member 1 (ACSL1), phosphatidylinositol 3-kinase (PI3K), phosphorylated (p)-PI3K, protein kinase B (AKT), and p-AKT. In human non-triple negative breast cancer tissues and cells, TSPAN31 expression was upregulated. TSPAN31 knockdown induced BC cell apoptosis, inhibited cell proliferation, invasion, migration, and fatty acid metabolism, and reduced the protein levels of FASN, SREBP1, ACSL1, p-PI3K/PI3K, and p-AKT/AKT. In contrast, TSPAN31 overexpression led to the opposite results. Additionally, the activator of PI3K (740 Y-P) attenuated the inhibition of TSPAN31 knockdown on fatty acid metabolism, proliferation, and invasion in BC cells. Through activation of fatty acid metabolism and PI3K/AKT pathway, TSPAN31 played a carcinogenic role in BC. For the mechanism of BC tumorigenesis, our study provides an interesting insight.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710803","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}

{"title":"Interferon-Inducible ADAR1 p150 Is Essential for the Survival of Oral Squamous Cell Carcinoma.","authors":"Pei San Yee, Annie Wai Yeeng Chai, Shi Mun Yee, Shiyin Ooi, Yee Hua Tan, Mathew J Garnett, Siew Kit Ng, Sok Ching Cheong","doi":"10.1002/mc.23910","DOIUrl":"https://doi.org/10.1002/mc.23910","url":null,"abstract":"<p><p>We identified ADAR1 as one of the top essential genes for oral squamous cell carcinoma (OSCC) survival from our genome-wide CRISPR/Cas9 screen in OSCC cell lines. In this study, we confirm that ADAR1-knockout (KO) inhibits cell viability and colony forming ability, and induces apoptosis. We report that IFN-β treatment sensitizes less-dependent cell lines to ADAR1 KO-induced cell lethality. Overexpression of ADAR1-p150, but not ADAR1-p110, rescued cell lethality upon ADAR1 KO, confirming that the IFN-inducible p150 is responsible for OSCC survival. Using a deaminase inactive mutant, we demonstrate that the editing function of ADAR1 is important for OSCC survival. Furthermore, we show that ADAR1 KO-induced cell death is mediated by both PKR and MDA5. We compute gene signatures of ADAR1 dependency in OSCC tumors, and found that those with high ADAR1 dependency score are associated with well or moderate differentiation, likely due to high PKR expression or activation. While a majority of ADAR1-dependent tumors exhibit a low T cell-inflamed gene expression profile, ADAR1 KO upregulates PD-L1, a marker of anti-PD1 response, indicating that ADAR1 inhibition may enhance immunotherapy response in OSCC. Collectively, these findings suggest that targeting ADAR1-p150 not only induces OSCC cell death but could induce a favorable response to anti-PD1.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710800","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}

{"title":"SOAT1 Activates NLRP3 Inflammasome to Promote Cancer-Related Lymphangiogenesis and Metastasis via IL-1β/IL-1R-1 Axis in Oral Squamous Cell Carcinoma.","authors":"Chengzhi Zhao, Yuhao Wang, Zhishen Jiang, Shengzhao Guo, Liru Hu, Jian Pan, Fan Dan","doi":"10.1002/mc.23907","DOIUrl":"https://doi.org/10.1002/mc.23907","url":null,"abstract":"<p><p>Oral squamous cell carcinoma (OSCC) is a prevalent type of cancer in the head and neck region, significantly impacting patient survival rates and quality of life. Lymph node (LN) metastasis is a lead contributor to the poor prognosis associated with OSCC. SOAT1 plays a critical role in cholesterol metabolism and has been implicated in various cancers, although its specific mechanisms in OSCC are poorly understood. Additionally, NLRP3 inflammasome has been identified as a factor that promotes cancer progression by influencing various processes involved in tumor development, with its activation linked to cancer metastasis. Lymphangiogenesis enhancing cancer metastasis has been identified in OSCC, while the molecule networks of regulating it remains unclear. In our study, we found that SOAT1 is overexpressed in OSCC and promotes proliferation, migration, and invasion of OSCC cells. Knockdown SOAT1 expression impaired OSCC progression both in vitro and in vivo, and reduced the rate of LN metastasis. RNA sequencing analysis revealed that NLRP3 is a downstream regulated by SOAT1, with NLRP3 inflammasome reactivation having recovered cancer malignancy inhibited by SOAT1 knockdown. Furthermore, we revealed that IL-1β, released by NLRP3 inflammasome activation, could directly bind to IL-1R-1 in lymphatic endothelial cells (LECs), and enhance tube formation capacity of LECs, indicating the potential role of NLRP3 inflammasome in promoting lymphangiogenesis and metastasis in OSCC. In conclusion, SOAT1 could promote OSCC malignancy and regulate the activation of NLRP3 inflammasome to increase the rate of lymphangiogenesis and cancer metastasis via IL-1β/IL-1R-1 axis in OSCC.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710802","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}