Periostin Promotes EMT Via Inhibition of RIN1-mediated Endocytosis of EGFR in Gliomas
Social Science Research Network(2021)
Abstract
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 differential 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 effects 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 effects of POSTN on the stability, endocytosis, and degradation of EGFR were examined by immunoblotting and immunofluorescence staining. Truncation mutation analysis was performed to investigate direct interactions between POSTN and EGFR. Immunohistochemical staining was carried out to confirm the clinical significance 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 findings 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 beneficial outcomes of glioma treatment.
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Key words
POSTN,EGFR,Endocytosis,Glioma,RIN1
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