期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 514, 期 4, 页码 1270-1277出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2019.05.096
关键词
Verbascoside; Glioblastoma (GBM); Epithelial-to-mesenchymal transition (EMT); Migration and invasion; c-Met; Ubiquitination
资金
- National Natural Science Foundation of China [81573774]
Verbascoside (VB), a glycosylated phenylpropanoid compound, is derived from the plant Syringe vulgaris (Oleaceae) and has been shown to have antitumor effects in multiple human cancers, including glioblastoma (GBM); however, the underlying mechanism has not been completely elucidated. Epithelial-tomesenchymal transition (EMT) is the pivotal event in tumor progression. c-Met, a receptor tyrosine kinase, plays an important role in GBM aggressiveness via promoting EMT. The current study aimed to explore whether VB suppresses c-Met-induced EMT and investigated the mechanism of c-Met degradation. We found that VB inhibited GBM cell growth and downregulated c-Met and the EMT markers (snail, vimentin, and zebl) in vitro and in an orthotopic xenograft mouse model. In addition, over-expressing c-Met in glioblastoma cells abolished the effects of VB on EMT. We also used a microscale thermophoresis (MST) assay to show that VB could directly bind to the c-Met protein, and we showed that VB degraded the c-Met protein via the ubiquitination-proteasome pathway. Our study is the first to identify a new mechanism for the anticancer effects of VB, namely, the inhibition of EMT by directly targeting c-Met; the inhibition of EMT results in c-Met protein degradation through the ubiquitinationproteasome pathway. Our current research indicates that VB is a potential agent to treat GBM via the ubiquitin-mediated degradation of c-Met. (C) 2019 Elsevier Inc. All rights reserved.
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