细胞外基质
转移
化学
表面等离子共振
癌细胞
下调和上调
整合素
细胞生物学
信号转导
细胞迁移
胶原受体
细胞粘附
生物化学
癌症研究
癌症
受体
细胞
生物
基因
纳米技术
纳米颗粒
材料科学
遗传学
作者
Ge Liu,Rui Liu,Yeqi Shan,Chaomin Sun
标识
DOI:10.1016/j.jbc.2021.101133
摘要
Many natural polysaccharides have significant anticancer activity with low toxicity, but the complex chemical structures make in-depth studies of the involved mechanisms extremely difficult. The purpose of this study was to investigate the effect of the marine bacterial exopolysaccharide (exopolysaccharide 11 [EPS11]) on liver cancer metastasis to explore the underlying target protein and molecular mechanism. We found that EPS11 significantly suppressed cell adhesion, migration, and invasion in liver cancer cells. Proteomic analysis showed that EPS11 induced downregulation of proteins related to the extracellular matrix-receptor interaction signaling pathway. In addition, the direct pharmacological target of EPS11 was identified as collagen I using cellular thermal shift assays. Surface plasmon resonance and pull-down assays further confirmed the specific binding of EPS11 to collagen I. Moreover, EPS11 was shown to inhibit tumor metastasis by directly modulating collagen I activity via the β1-integrin-mediated signaling pathway. Collectively, our study demonstrated for the first time that collagen I could be a direct pharmacological target of polysaccharide drugs. Moreover, directly targeting collagen I may be a promising strategy for finding novel carbohydrate-based drugs.
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