Journal of Cancer最新文献

{"title":"Risk Prediction of Myelosuppression Following First-line Chemotherapy in Colorectal Cancer.","authors":"Yanyuan Du, Yuming Liu, Ruiying Fang, Liu Cai, Ying Song, Susu Ma, Huibo Yu, Jin Gao, Hongtai Xiong, Hanyue Zhang, Baihui Li, Honggang Zheng","doi":"10.7150/jca.104412","DOIUrl":"10.7150/jca.104412","url":null,"abstract":"<p><p><b>Background:</b> Colorectal cancer (CRC) is a leading cause of cancer-related deaths, with over 1.9 million new cases and 904,000 deaths in 2022. Chemotherapy is a primary treatment for CRC but often leads to myelosuppression, significantly affecting treatment efficacy and patient outcomes. Predictive tools for chemotherapy-induced myelosuppression are currently lacking. <b>Methods:</b> This retrospective study analyzed 855 CRC patients from Guang'anmen Hospital who received first-line chemotherapy (CapeOx, FOLFOX, FOLFIRI) between April 2020 and July 2024. Patients were divided into training (684) and validation (171) groups. Univariate analysis, LASSO regression, and multivariable logistic regression identified risk factors for myelosuppression, and a predictive nomogram was developed and validated using ROC curves, calibration curves, and decision curve analysis. Propensity score matching (PSM) was employed to minimize baseline differences between groups, followed by multivariate logistic regression analysis on the post-PSM data. <b>Results:</b> The incidence of myelosuppression was similar in both groups (33.04% vs. 32.16%). Significant predictors included age, smoking, diabetes, BMI, tumor location, lung metastasis, albumin (ALB) levels, and carcinoembryonic antigen (CEA) levels. The nomogram demonstrated good predictive performance with AUC values of 0.78 and 0.80 for the training and validation groups, respectively, showing consistent and clinically useful predictions. PSM further validated the robustness of the model, confirming BMI as a consistently significant predictor of myelosuppression. <b>Conclusions:</b> The study identified key risk factors for chemotherapy-induced myelosuppression in CRC patients and developed a nomogram for prediction. This tool can help clinicians assess risk and guide treatment decisions. Limitations include potential selection bias and the need for external validation in diverse populations. Future studies should further refine and validate this predictive model.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 4","pages":"1379-1396"},"PeriodicalIF":3.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics analysis of core E3 ubiquitin ligase identifies prognostic biomarkers associated with immune infiltration and drug sensitivity in lung adenocarcinoma.","authors":"Yuan-Xiang Shi, Jia Wang, Zhen-Lin Jiang, Jian-Hua Yan","doi":"10.7150/jca.104837","DOIUrl":"10.7150/jca.104837","url":null,"abstract":"<p><p><b>Background:</b> Ubiquitination is involved in several tumor immunomodulatory processes, and targeting E3 ubiquitin ligases has substantial potential in cancer therapy. <b>Methods:</b> In this study, the key E3 ubiquitin ligases involved in regulating the malignant progression of LUAD were studied. We first systematically investigated the expression landscape, prognosis, immune infiltration, drug sensitivity, and potential molecular mechanisms of these hub genes in LUAD. <i>CDC20</i> was localized by immunofluorescence analysis in tumor cell lines, and its expression level was determined by immunohistochemistry on tissue chips. Single-cell analysis and spatial transcriptomics were used to determine <i>CDC20</i> expression in multiple cell types. Molecular docking was performed via computer simulation to verify the ability of drugs to bind to target genes. <b>Results:</b> We found that these hub genes are specifically overexpressed in LUAD and are associated with poor patient prognosis. All five E3 ubiquitin ligase genes were negatively correlated with B cells and dendritic cells but positively related to neutrophil immune infiltration. In addition, analysis of the CTRP and GDSC databases revealed that the sensitivity to multiple antitumor drugs increased when <i>CCNF</i> was highly expressed. GSEA enrichment analysis demonstrated that the G2M_CHECKPOINT, MTORC1_SIGNALING, OXIDATIVE_PHOSPHORYLATION, and GLYCOLYSIS signaling pathways were enriched when <i>CDC20</i> was highly expressed. Further correlation analysis indicated that <i>CDC20</i> was positively correlated with the expression of the key genes mTOR, S6K1, and 4E-BP1 and the autophagy-related gene ULK1 in the mTORC1 signaling pathway. <b>Conclusions:</b> These key E3 ubiquitin ligases serve as potential molecular biomarkers for predicting the prognosis, immune response, and drug sensitivity of LUAD patients.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 4","pages":"1363-1378"},"PeriodicalIF":3.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HER4 Promotes Osteosarcoma Progression and Predicts Poor Prognosis through the PTEN-PI3K/AKT Pathway: Retraction.","authors":"Kun Ma, Chuan Zhang","doi":"10.7150/jca.110321","DOIUrl":"https://doi.org/10.7150/jca.110321","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.7150/jca.62787.].</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 4","pages":"1347"},"PeriodicalIF":3.3,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring breast cancer associated-gene panel for next-generation sequencing and identifying new, pathogenic variants in breast cancer from western China.","authors":"Jingliang Cheng, Binghui Song, Chunli Wei, Lianmei Zhang, Xiaoyan Liu, Lisha Yang, Singkome Tima, Sawitree Chiampanichayakul, Xiuli Xiao, Songyot Anuchapreeda, Junjiang Fu","doi":"10.7150/jca.101911","DOIUrl":"10.7150/jca.101911","url":null,"abstract":"<p><p>Breast cancer (BC) is the most frequently diagnosed and the leading cause of cancer-related deaths among women worldwide. It is crucial to develop a cost-effective BC genetic panel for detection and diagnosis. In this study, tissue samples from 52 BC patients and peripheral blood samples from 18 healthy volunteers were collected in western China, followed by gDNA extraction. H&E and IHC analysis were employed to detect the expression of invasive BC tissues. We analyzed data using public databases such as COSMIC/ClinVar/HGMD along with our own previously published data and queried commercial BC panels to select high-risk genes. Using Illumina DesignStudio, gene panel primers consisting of 13 genes were designed with 696 primer pairs. The specificity of all primers was validated through common PCR assays. Once the gene panel was completed, multiple polymerase chain reactions (MPCR) were performed using the designed panel primers. The resulting MPCR products were purified to enrich them as library templates. Subsequently, after passing quality tests for library integrity assessment, Next-generation sequencing (NGS) was conducted. Through bioinformatics analysis of the NGS data, 4,571 variants were identified in the annotation files from 52 samples, classified into different types. Among these variants, 358 (approximately 7.8%) were newly discovered and distributed across 11 genes in 52 patients without in the ExAC database. The <i>KMT2C</i> gene exhibited the highest frequency of variants, presenting in 83.0% of 52 patient samples. Variants in <i>BRCA2</i> (71%), <i>BRCA1</i> (48%), <i>PALB2</i> (40%), <i>PIK3CA</i> (23%), and <i>RNF40</i> (21%) genes were found in over 20% of patients. Additionally, variants were observed in the <i>AKT1</i> (12%), <i>ERBB2</i> (10%), <i>ESR1</i> (8%), <i>TWIST1</i> (8%), and <i>PIK3R1</i> (4%) genes. Further analysis using PolyPhen-2, SIFT, CADD, and Mutation Taster tools analysis showed that out of these new variants, 49 (49/358) had potential pathogenic effects on protein functions and structure across 52 patients. Consequently, a high-risk gene panel has been preliminarily established for early detection/diagnosis that will contribute to earlier prevention and treatment strategies for individuals with BC, particularly those residing in developing or underdeveloped countries. The identification of novel pathogenic variants within our cohort not only expands knowledge regarding genetic diagnosis applications for BC patients but also facilitates genetic counseling services for affected individuals and their families.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 4","pages":"1281-1295"},"PeriodicalIF":3.3,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoadjuvant Chemotherapy Can Effectively Avoid Unnecessary Extended Resection for Gastric Cancer with Clinical Evidence of Duodenum or Pancreas Head Involvement.","authors":"Qianna Jin, Jiaqing Cao, Guobin Wang, Nan He","doi":"10.7150/jca.105534","DOIUrl":"10.7150/jca.105534","url":null,"abstract":"<p><p><b>Purpose:</b> This study aims to compare the efficacy of two treatment strategies for gastric cancer with clinical evidence of pancreatic head or duodenal involvement: gastrectomy combined with pancreaticoduodenectomy (GPD) and neoadjuvant chemotherapy followed by surgery (NCS). <b>Methods:</b> A retrospective analysis of patient data from January 2012 to January 2022 was conducted to evaluate the outcomes of these two treatment strategies. <b>Results:</b> The study included 284 patients, comprising 78 in the GPD group and 206 in the NCS group. In the NCS group, 119 patients required extended pancreaticoduodenectomy, a significantly smaller proportion compared to the GPD group (p < 0.001). The NCS group successfully avoided unnecessary extended pancreaticoduodenectomy. In contrast, 15 patients in the GPD group underwent surgery despite postoperative pathological confirmation of no pancreatic head or duodenal involvement (p < 0.001). The incidence of Clavien-Dindo grade ≥ IIIb complications was significantly greater in the GPD group than in the NCS group (10.3% vs. 3.3%, p = 0.034). Overall survival was significantly longer in the NCS group, with a median of 25 months compared to 20 months in the GPD group (p = 0.0005). Multivariate Cox regression analysis revealed that tumor diameter ≥7 cm and N3 stage were independent adverse prognostic factors. <b>Conclusion:</b> Neoadjuvant chemotherapy is recommended for patients with gastric cancer presenting clinical evidence of pancreatic head or duodenal involvement. This approach reduces unnecessary extended surgeries, lowers complication rates, and improves overall survival.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 4","pages":"1181-1188"},"PeriodicalIF":3.3,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The clinical impact of galectin-8 in drug resistant breast cancer.","authors":"Yi-Chung Chien, Jia-Yan Wu, Chi-Chun Pang, Ruey-Hwang Chou, Yung-Luen Yu","doi":"10.7150/jca.104000","DOIUrl":"10.7150/jca.104000","url":null,"abstract":"<p><p>Breast cancer remains the leading cause of cancer-related mortality among women globally. A significant challenge in lowering breast cancer death rates is multidrug resistance. This resistance arises through various mechanisms, such as heightened drug efflux, improved DNA repair, escape from senescence, epigenetic modifications, tumor heterogeneity, alterations in the tumor microenvironment (TME), and the epithelial-to-mesenchymal transition (EMT). These factors collectively make overcoming drug resistance particularly difficult. Therefore, in this study, we analyzed data from The Cancer Genome Atlas (TCGA) and identified a novel gene, galectin-8, which plays a critical regulatory role in breast cancer progression. Gene Set Enrichment Analysis (GSEA) further revealed that galectin-8 is involved in modulating drug resistance in breast cancer. To validate this finding, we conducted a mass assay comparing drug-resistant triple-negative breast cancer (TNBC) cell lines with control groups. Our results demonstrated a significant increase in galectin-8 expression in the drug-resistant cells, with statistically significant differences observed. In addition, we found that reducing galectin-8 expression in drug-resistant cell lines not only reinstated the effectiveness of anticancer drugs but also suppressed tumor cell proliferation and migration. Therefore, our findings highlight the significant prognostic and therapeutic potential of galectin-8, emphasizing the importance of future research to explore targeted therapeutic strategies in breast cancer.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 4","pages":"1296-1309"},"PeriodicalIF":3.3,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment of a Basement Membrane-Related Prognosis Model and Characterization of Tumor Microenvironment Infiltration in Acute Myeloid Leukemia.","authors":"Zongsi Zhu, Yuedong Zhao, Ping Li","doi":"10.7150/jca.108041","DOIUrl":"10.7150/jca.108041","url":null,"abstract":"<p><p><b>Background:</b> Basement membrane is a special component of extracellular matrix of epithelial and endothelial tissues, which can maintain their normal morphologies and functions. It can also participate in tumor progression and affect tumor treatment. However, the roles of basement membrane-related genes (BMGs) in acute myeloid leukemia (AML) remain unknown. <b>Material and methods:</b> We downloaded the data of AML and normal samples from TCGA, GTEx, and GEO. Then, we performed bioinformatics analysis to identify differential BMGs. We calculated the risk score of the training cohort and divided it into two risk groups. In addition, we also introduced external cohorts, serving as validation cohorts, to estimate the accuracy of risk score. A nomogram was established based on the risk score and clinicopathological characteristics to predict the prognosis. Based on BMGs, AML patients of TCGA were clustered into 2 subtypes. To investigate the biological features and the association between immune cells and TME, we utilized GSVA to assess pathway enrichment and ssGSEA to quantify the levels of immune cell infiltration across samples. <b>Results:</b> We obtained 3 differential BMGs between AML and normal samples. The training cohort was divided into high- and low-risk groups based on the risk score. The Kaplan-Meier survival analysis indicated that the two groups had significant differences. The nomogram could be used to predict the survival outcomes of AML patients. Based on the clustering result, we found significant differences between the two gene clusters. Sankey's diagram suggested that cluster B was associated with the high-risk group and poor prognosis. GSVA analysis showed that cluster B was also related to the upregulation of intercellular and intracellular signal transduction pathways. In TME, resting mast cells, follicular helper T cells, and plasma cells decreased while monocytes increased in the high-risk group. In addition, the high-risk group was more sensitive to BTK and AKT inhibitors. <b>Conclusion:</b> Our study indicated that the nomogram model of BMGs could predict the prognosis of AML patients. Meanwhile, BMGs were correlated with immune TME in AML. A correct and comprehensive assessment of the mechanisms of BMGs in individuals will help guide more effective treatment.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 4","pages":"1228-1242"},"PeriodicalIF":3.3,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TGF-β secreted by cancer cells-platelets interaction activates cancer metastasis potential by inducing metabolic reprogramming and bioenergetic adaptation.","authors":"Chunlian Zhong, Weiyu Wang, Yinyin Yao, Shu Lian, Xiaodong Xie, Judan Xu, Shanshan He, Lin Luo, ZhouZhou Ye, Jiajie Zhang, Mingqing Huang, Guihua Wang, Yanhong Wang, Yusheng Lu, Chengbin Fu","doi":"10.7150/jca.103757","DOIUrl":"10.7150/jca.103757","url":null,"abstract":"<p><p>Metastasis is the leading cause of cancer-related deaths and poses a treatment challenge. Although studies have shown the importance of epithelial-mesenchymal transition (EMT) and metabolic reprogramming during cancer metastasis, the link between EMT and metabolic reprogramming, as well as the underlying molecular mechanisms by which both mediate cancer cell invasion and metastasis have not been elucidated. Here, we observed that interactions between platelets and cancer cells promote the secretion of TGF-β, thereby initiating EMT, promoting the invasion, and altering the metastatic and metabolic potential of colon cancer cells. TGF-β activates the AKT signaling pathway to enhance HK1 and HK2 expression in cancer cells, leading to increased glucose consumption, ATP production, and precise modulation of cell cycle distribution. In an energy-deficient model induced by oxidative phosphorylation (OXPHOS) inhibition with oligomycin A, TGF-β-induced highly metastatic HCT116 (H-HCT116) cells adapt by upregulating HK expression and glycolytic metabolism, while concurrently decreasing cell proliferation to conserve energy for survival. Mechanistically, H-HCT116 cells regulate cell division rates by downregulating CDK2, CDK4, and Cyclin D1 protein expression and upregulating p21 expression. Furthermore, H-HCT116 cells display enhanced motility, which is linked to increased mitochondrial metabolic activity. These findings indicated that cancer cells-platelets interaction secreted TGF-β activates cancer metastasis potential by inducing metabolic reprogramming and bioenergetic adaptation. The present study provides new insights into the adaptive strategies of highly metastatic cancer cells under adverse conditions and indicates that targeting glycolysis and metabolic reprogramming could serve as a viable approach to prevent cancer metastasis.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 4","pages":"1310-1323"},"PeriodicalIF":3.3,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Nomogram for the Prediction and Evaluation of Prognosis in Patients with Early-onset Kidney Cancer: a Population-based Study.","authors":"Dingyang Lv, Qiwei Wang, Ke Sun, Jinshuai Li, Huiyu Zhou, Jie Wen, Weibing Shuang","doi":"10.7150/jca.104569","DOIUrl":"10.7150/jca.104569","url":null,"abstract":"<p><p><b>Background:</b> Early-onset kidney cancer (EOKC) is often associated with genetic factors and a high risk of metastasis. However, there is a lack of accurate prediction models for the prognosis of EOKC. The aim of this study is to establish an effective nomogram for predicting and evaluating the prognosis of patients with EOKC. <b>Methods:</b> The patients with EOKC were selected from the latest SEER database during 2004-2015. Patients between 2004 and 2014 were randomly divided into a training cohort and a validation cohort at a ratio of 7:3, and patients in 2015 were used for temporal external validation. Additionally, we included patients from First Hospital of Shanxi Medical University between 2013 and 2021 for spatial external validation. The performance of the nomogram was assessed using the concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Patients were stratified based on the nomogram, and Kaplan-Meier (KM) curves were plotted to compare the survival probability of patients. <b>Results:</b> In the temporal and spatial external validation cohort, the C-index of the nomogram for OS was 0.872 and 0.875, respectively, and the C-index of the nomogram for CSS were 0.872 and 0.851, respectively. In the temporal external validation cohort, the 1-year, 3-year and 5-year AUC of the nomogram for OS were 0.906, 0.899 and 0.876, respectively. In addition, the AUC showed that the nomogram had also high predictive ability for CSS. The calibration curves and DCA also indicated that the nomogram had a strong clinical utility. The KM curve revealed that patients in the low-risk group had a better prognosis than those in the high-risk group. <b>Conclusion:</b> Our study developed a novel high-performance nomogram for assessing the prognosis of patients with EOKC, and it has great potential for clinicians to assess patient prognosis and formulate effective intervention and follow-up strategies.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 4","pages":"1189-1201"},"PeriodicalIF":3.3,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matrix stiffness regulates NPC invasiveness by modulating a mechanoresponsive TRPV4-Nox4-IL-8 signaling axis.","authors":"Peng Zhang, Dunhui Yang, Kang Li, Jin Zhang, Zhen Wang, Fang Ma, Xianqin Liao, Shibo Ma, Xianhai Zeng, Xiangmin Zhang","doi":"10.7150/jca.104235","DOIUrl":"10.7150/jca.104235","url":null,"abstract":"<p><p>Matrix stiffness is a critical determinant of tumorigenesis and cancer progression. Transient receptor potential vanilloid 4 (TRPV4), a mechanosensitive calcium channel, regulates angiogenesis and stromal stiffness in various tumors. However, it is unclear whether matrix stiffness regulates the invasiveness of nasopharyngeal carcinoma (NPC) cells through TRPV4. In this study, we found that increased matrix stiffness of NPC tissues correlated with advanced tumor stages. Furthermore, simulation of high matrix stiffness <i>in vitro</i> upregulated TRPV4, and increased the migration, invasion, and epithelial mesenchymal transition (EMT) of NPC cells. Knockdown or pharmacological inhibition of TRPV4 significantly suppressed the calcium influx in NPC cells, and inhibited their invasiveness and EMT under high-stiffness conditions. Mechanistically, TRPV4 modulated the invasiveness of NPC cells in response to matrix stiffness via the NOX4/IL-8 axis. Notably, TRPV4 and IL-8 levels were significantly increased in the high-stiffness NPC tissues, and showed a positive correlation. Taken together, matrix stiffness promotes the malignant progression of NPC cells through the activation of the TRPV4/NOX4/IL-8 axis, which could be explored further as a potential target for NPC therapy.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 4","pages":"1324-1334"},"PeriodicalIF":3.3,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}