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

Purpose:Approximately 1/3 of brain tumors are gliomas.Previous 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 unclear.Methods: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 samples.Quantitative real-time PCR(qRT-PCR)was used to measure the expression of POSTN in tissues and cells.The 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 vivo.The efects of POSTN on the stability,endocytosis,and degradation of EGFR were examined by immunoblotting and immunofuorescence staining.Truncation mutation analysis was performed to investigate direct interactions between POSTN and EGFR.Immunohistochemical staining was carried out to confrm the clinical signifcance of POSTN.Results:Overexpression of POSTN induced epithelial-to-mesenchymal transition(EMT)in glioma cells in vivo and in vitro.Mechanistically,POSTN downregulation inhibited EGFR signaling by promoting EGFR endocytosis and degradation.In addition,POSTN was found to bind to EGFR and RIN1,inhibiting EGFR endocytosis and degradation and thus activating the PI3K-Akt signaling pathway.Conclusion: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 pathway.Targeting POSTN/EGFR/RIN1 interactions may guarantee benefcial outcomes of glioma treatment.