Chondroitin sulfate synthase 1 enhances proliferation of glioblastoma by modulating PDGFRA stability

doi:10.1038/s41389-020-0197-0

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/24528

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/24528

Title:	Chondroitin sulfate synthase 1 enhances proliferation of glioblastoma by modulating PDGFRA stability
Authors:	Liao, WC;Liao, CK;Tseng, TJ;Ho, YJ;Chen, YR;Lin, KH;Lai, TJ;Lan, CT;Wei, KC;Liu, CH
Date:	2020
Issue Date:	2022-08-09T08:03:50Z (UTC)
Publisher:	NATURE PUBLISHING GROUP
ISSN:	2157-9024
Abstract:	Chondroitin sulfate synthases, a family of enzyme involved in chondroitin sulfate (CS) polymerization, are dysregulated in various human malignancies, but their roles in glioma remain unclear. We performed database analysis and immunohistochemistry on human glioma tissue, to demonstrate that the expression of CHSY1 was frequently upregulated in glioma, and that it was associated with adverse clinicopathologic features, including high tumor grade and poor survival. Using a chondroitin sulfate-specific antibody, we showed that the expression of CHSY1 was significantly associated with CS formation in glioma tissue and cells. In addition, overexpression of CHSY1 in glioma cells enhanced cell viability and orthotopic tumor growth, whereas CHSY1 silencing suppressed malignant growth. Mechanistic investigations revealed that CHSY1 selectively regulates PDGFRA activation and PDGF-induced signaling in glioma cells by stabilizing PDGFRA protein levels. Inhibiting PDGFR activity with crenolanib decreased CHSY1-induced malignant characteristics of GL261 cells and prolonged survival in an orthotopic mouse model of glioma, which underlines the critical role of PDGFRA in mediating the effects of CHSY1. Taken together, these results provide information on CHSY1 expression and its role in glioma progression, and highlight novel insights into the significance of CHSY1 in PDGFRA signaling. Thus, our findings point to new molecular targets for glioma treatment.
URI:	http://dx.doi.org/10.1038/s41389-020-0197-0 https://www.webofscience.com/wos/woscc/full-record/WOS:000511375800001 https://ir.csmu.edu.tw:8080/handle/310902500/24528
Relation:	ONCOGENESIS ,2020 ,v9 ,issue 2
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

Files in This Item:

File	Description	Size	Format
index.html		0Kb	HTML	250	View/Open

Loading...