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.

中文翻译：

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海洋细菌胞外多糖EPS11通过直接靶向I型胶原抑制肝癌细胞的迁移和侵袭。

许多天然多糖具有显着的抗癌活性和低毒性，但其复杂的化学结构使得对其机制的深入研究极为困难。本研究的目的是研究海洋细菌胞外多糖（胞外多糖 11 [EPS11]）对肝癌转移的影响，以探讨潜在的靶蛋白和分子机制。我们发现EPS11显着抑制肝癌细胞的细胞粘附、迁移和侵袭。蛋白质组学分析表明，EPS11 诱导与细胞外基质-受体相互作用信号通路相关的蛋白质下调。此外，EPS11 的直接药理学靶标被鉴定为使用细胞热位移测定的胶原蛋白 I。表面等离子共振和下拉测定进一步证实了 EPS11 与胶原蛋白 I 的特异性结合。此外，EPS11 显示通过 β1 整合素介导的信号通路直接调节胶原蛋白 I 活性来抑制肿瘤转移。总的来说，我们的研究首次证明胶原蛋白 I 可以成为多糖药物的直接药理学靶点。此外，直接靶向 I 型胶原蛋白可能是寻找新型碳水化合物药物的有前途的策略。