中山醫學大學機構典藏 CSMUIR:Item 310902500/24528
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    题名: Chondroitin sulfate synthase 1 enhances proliferation of glioblastoma by modulating PDGFRA stability
    作者: Liao, WC;Liao, CK;Tseng, TJ;Ho, YJ;Chen, YR;Lin, KH;Lai, TJ;Lan, CT;Wei, KC;Liu, CH
    日期: 2020
    上传时间: 2022-08-09T08:03:50Z (UTC)
    出版者: NATURE PUBLISHING GROUP
    ISSN: 2157-9024
    摘要: 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
    關聯: ONCOGENESIS ,2020 ,v9 ,issue 2
    显示于类别:[中山醫學大學研究成果] 期刊論文

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