Periostin promotes EMT via inhibition of RIN1-mediated endocytosis of EGFR in gliomas

作     者：Fengqi Zhou Tianfu Yu Fan Xiao Binbin Wang Wei Tian Ran Xu Xiaochun Zhao Ailiang Zeng Ning Liu Yingyi Wang Yongping You Junxia Zhang 

作者机构：Department of NeurosurgeryThe First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029Jiangsu ProvinceChina Department of NeurosurgeryThe Affiliated hospital of Nanjing University Medical SchoolNanjingJiangsu ProvinceChina Department of NeurosurgeryAffiliated Hospital of Jiangnan UniversityWuxiJiangsu ProvinceChina Department of NeurosurgeryUniversity of Oklahoma Health Science CenterOklahoma CityOKUSA Department of Cancer BiologyThe University of Texas MD Anderson Cancer CenterHoustonTexasUSA 

出 版 物：《Holistic Integrative Oncology》 (整合肿瘤学（英文）)

年 卷 期：2022年第1卷第1期

页      面：255-267页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by grants from National Natural Science Foundation of China (81772682) the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) 

主　　题：POSTN EGFR Endocytosis Glioma RIN1 

摘      要：Purpose:Approximately 1/3 of brain tumors are *** glioma-related studies have reported increased expression of periostin(POSTN)in these cancerous tissues,but the role and mechanism of POSTN in glioma development remain ***:Nanoscale liquid chromatography coupled with tandem mass spectrometry(nano LC-MS/MS)and RNA sequencing were used to identify diferential protein and mRNA expression in clinical glioma *** real-time PCR(qRT-PCR)was used to measure the expression of POSTN in tissues and *** efects of POSTN on glioma cell migration and invasion were examined using wound healing,Transwell,and three-dimensional spheroid assays in vitro and a nude mouse xenograft model in *** efects of POSTN on the stability,endocytosis,and degradation of EGFR were examined by immunoblotting and immunofuorescence *** mutation analysis was performed to investigate direct interactions between POSTN and *** staining was carried out to confrm the clinical signifcance of ***:Overexpression of POSTN induced epithelial-to-mesenchymal transition(EMT)in glioma cells in vivo and in ***,POSTN downregulation inhibited EGFR signaling by promoting EGFR endocytosis and *** addition,POSTN was found to bind to EGFR and RIN1,inhibiting EGFR endocytosis and degradation and thus activating the PI3K-Akt signaling ***:These fndings indicate the mechanism by which the POSTN/EGFR/RIN1 axis inhibits EGFR endocytosis and degradation,resulting in glioma cell EMT through the PI3K-AKT signaling *** POSTN/EGFR/RIN1 interactions may guarantee benefcial outcomes of glioma treatment.