Carbohydrate-to-carbohydrate interactions between α2,3-linked sialic acids on α2 integrin subunits and asialo-GM1 underlie the bone metastatic behaviour of LNCAP-derivative C4-2B prostate cancer cells.
Carbohydrate-to-carbohydrate interactions between α2,3-linked sialic acids on α2 integrin subunits and asialo-GM1 underlie the bone metastatic behaviour of LNCAP-derivative C4-2B prostate cancer cells.
复制标题
α2 整合素亚基上的 α2,3 连接唾液酸与 asialo-GM1 之间的碳水化合物与碳水化合物之间的相互作用是 LNCAP 衍生 C4-2B 前列腺癌细胞骨转移行为的基础。
DOI：
10.1042/bsr20140096
复制
发表时间：
2014-09-17
影响因子：
4
通讯作者：
Steelant WF
中科院分区：
文献类型：
--
作者：
Van Slambrouck S;Groux-Degroote S;Krzewinski-Recchi MA;Cazet A;Delannoy P;Steelant WF
蛋白质、脂质和碳水化合物之间的复杂相互作用可以改变表型，并且被认为在肿瘤转移中具有关键作用。我们以前的研究表明，GSL（鞘糖脂）AsGM 1（无唾液酸GM 1）（缺乏α 2，3-连接的唾液酸）和α2β1整联蛋白受体的复合物负责C4-2B前列腺癌细胞的转移行为。在此，我们确定并解决了前列腺癌进展过程中唾液酸化变化的功能意义。我们观察到α2β1整联蛋白受体α2亚基上α 2，3-连接唾液酸残基的增加，与α 2，3-ST（唾液酸转移酶），特别是ST 3GAL 3的基因表达增加相关。α2亚基的细胞表面α 2，3-唾液酸化是整合素α2β1依赖性细胞粘附于I型胶原所必需的，整合素受体上相同的α 2，3-连接的唾液酸残基负责与AsGM 1的碳水化合物部分的相互作用，解释了AsGM 1和α2β1整合素受体之间的复合物形成。这些结果提供了新的见解唾液酸的组织和功能的重要膜组件在入侵和转移过程中的作用。
Complex interplays among proteins, lipids and carbohydrates can alter the phenotype and are suggested to have a crucial role in tumour metastasis. Our previous studies indicated that a complex of the GSLs (glycosphingolipids), AsGM1 (asialo-GM1), which lacks α2,3-linked sialic acid, and α2β1 integrin receptors is responsible for the metastatic behaviour of C4-2B prostate cancer cells. Herein, we identified and addressed the functional significance of changes in sialylation during prostate cancer progression. We observed an increase in α2,3-linked sialic acid residues on α2 subunits of α2β1 integrin receptors, correlating with increased gene expression of α2,3-STs (sialyltransferases), particularly ST3GAL3. Cell surface α2,3-sialylation of α2 subunits was required for the integrin α2β1-dependent cell adhesion to collagen type I and the same α2,3-linked sialic acid residues on the integrin receptor were responsible for the interaction with the carbohydrate moiety of AsGM1, explaining the complex formation between AsGM1 and α2β1 integrin receptors. These results provide novel insights into the role of sialic acids in the organization and function of important membrane components in invasion and metastatic processes.