Kunhua Yao , Mingbiao Yang , Mi Shu , Tian Wang , Dan Gao , Liqi Zhou , Guangwei Wang , Zaiqi Zhang , Jiefu Tang
{"title":"SOX4 促进胶质母细胞瘤的血管异常,是改善给药的新靶点","authors":"Kunhua Yao , Mingbiao Yang , Mi Shu , Tian Wang , Dan Gao , Liqi Zhou , Guangwei Wang , Zaiqi Zhang , Jiefu Tang","doi":"10.1016/j.tranon.2024.102120","DOIUrl":null,"url":null,"abstract":"<div><p>Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults with dismal prognosis. Vascular abnormality is a hallmark of GBM, and aggravates diseases progression by increasing hypoxia, inducing life-threaten edema and hindering drug delivery. Nonetheless, the intricate mechanism underlying vascular abnormality remains inadequately understood. Here, we revealed a key role of SOX4 on vascular abnormality in GBM. SOX4 expression was increased in endothelial cells (ECs) from human brain tumors compared with ECs from paired normal brain tissue. Knockdown of SOX4 in mouse brain ECs restrained cell migration and proliferation. Furthermore, <em>in vitro</em> suppression of SOX4 in brain ECs and <em>in vivo</em> conditional knockout of SOX4 in tumor ECs led to the downregulation of genes linked with vascular abnormality. Notably, specific depletion of SOX4 in ECs enhanced drug delivery and sensitive tumor to chemotherapeutic drugs in GBM. Taken together, these results demonstrated that SOX4 is a novel regulator for tumor angiogenesis and vascular abnormality in GBM. Our findings identify SOX4 as a potential vascular therapeutic target to improve drug delivery for GBM treatment.</p></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"50 ","pages":"Article 102120"},"PeriodicalIF":5.0000,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S193652332400247X/pdfft?md5=8f18ff30a8069e57f4498f743ca5c0b4&pid=1-s2.0-S193652332400247X-main.pdf","citationCount":"0","resultStr":"{\"title\":\"SOX4 promotes vascular abnormality in glioblastoma and is a novel target to improve drug delivery\",\"authors\":\"Kunhua Yao , Mingbiao Yang , Mi Shu , Tian Wang , Dan Gao , Liqi Zhou , Guangwei Wang , Zaiqi Zhang , Jiefu Tang\",\"doi\":\"10.1016/j.tranon.2024.102120\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults with dismal prognosis. Vascular abnormality is a hallmark of GBM, and aggravates diseases progression by increasing hypoxia, inducing life-threaten edema and hindering drug delivery. Nonetheless, the intricate mechanism underlying vascular abnormality remains inadequately understood. Here, we revealed a key role of SOX4 on vascular abnormality in GBM. SOX4 expression was increased in endothelial cells (ECs) from human brain tumors compared with ECs from paired normal brain tissue. Knockdown of SOX4 in mouse brain ECs restrained cell migration and proliferation. Furthermore, <em>in vitro</em> suppression of SOX4 in brain ECs and <em>in vivo</em> conditional knockout of SOX4 in tumor ECs led to the downregulation of genes linked with vascular abnormality. Notably, specific depletion of SOX4 in ECs enhanced drug delivery and sensitive tumor to chemotherapeutic drugs in GBM. Taken together, these results demonstrated that SOX4 is a novel regulator for tumor angiogenesis and vascular abnormality in GBM. Our findings identify SOX4 as a potential vascular therapeutic target to improve drug delivery for GBM treatment.</p></div>\",\"PeriodicalId\":48975,\"journal\":{\"name\":\"Translational Oncology\",\"volume\":\"50 \",\"pages\":\"Article 102120\"},\"PeriodicalIF\":5.0000,\"publicationDate\":\"2024-09-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S193652332400247X/pdfft?md5=8f18ff30a8069e57f4498f743ca5c0b4&pid=1-s2.0-S193652332400247X-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Translational Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S193652332400247X\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational Oncology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S193652332400247X","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
SOX4 promotes vascular abnormality in glioblastoma and is a novel target to improve drug delivery
Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults with dismal prognosis. Vascular abnormality is a hallmark of GBM, and aggravates diseases progression by increasing hypoxia, inducing life-threaten edema and hindering drug delivery. Nonetheless, the intricate mechanism underlying vascular abnormality remains inadequately understood. Here, we revealed a key role of SOX4 on vascular abnormality in GBM. SOX4 expression was increased in endothelial cells (ECs) from human brain tumors compared with ECs from paired normal brain tissue. Knockdown of SOX4 in mouse brain ECs restrained cell migration and proliferation. Furthermore, in vitro suppression of SOX4 in brain ECs and in vivo conditional knockout of SOX4 in tumor ECs led to the downregulation of genes linked with vascular abnormality. Notably, specific depletion of SOX4 in ECs enhanced drug delivery and sensitive tumor to chemotherapeutic drugs in GBM. Taken together, these results demonstrated that SOX4 is a novel regulator for tumor angiogenesis and vascular abnormality in GBM. Our findings identify SOX4 as a potential vascular therapeutic target to improve drug delivery for GBM treatment.
期刊介绍:
Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.