Interactions of mucins with the Tn or Sialyl Tn cancer antigens including MUC1 are due to GalNAc-GalNAc interactions.
Interactions of mucins with the Tn or Sialyl Tn cancer antigens including MUC1 are due to GalNAc-GalNAc interactions.
复制标题
粘蛋白与 Tn 或唾液酸 Tn 癌抗原（包括 MUC1）的相互作用是由于 GalNAc-GalNAc 相互作用所致。
DOI：
10.1093/glycob/cww065
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发表时间：
2016
期刊：
影响因子：
4.3
通讯作者：
Haugstad KE
中科院分区：
文献类型：
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作者：
Haugstad KE
利用光学镊子（OT）研究了具有Tn （GalNAcα1-Ser/Thr）或STn （NeuNAcα2-6GalNAcα1-Ser/Thr）癌症标志物的粘蛋白增强自相互作用的分子机制。所检测的粘蛋白包括含有Tn表位的改性猪上颌下粘蛋白（Tn- psm），含有STn表位的羊上颌下粘蛋白（STn- osm），以及含有Tn和STn表位的重组MUC1类似物。将粘蛋白固定在聚苯乙烯珠上的OT实验显示，所有粘蛋白具有相同的自相互作用特性。具有多个GalNAc修饰的合成聚合物也观察到相同的结合强度和能量景观特征。没有固定粘蛋白的聚苯乙烯微球没有自相互作用，也没有与粘蛋白修饰的聚苯乙烯微球相互作用。综上所述，实验数据表明，在这些分子中，GalNAc残基介导了独立于锚定聚合物主链的相互作用。此外，GalNAc-GalNAc相互作用似乎与修饰STn表位的粘蛋白的自相互作用有关。因此，Tn-MUC1和STn-MUC1在两个表位上都通过GalNAc残基介导的自相互作用，提示其可能在癌症中起分子作用。含有T （Galβ1-3GalNAcα1-Ser/Thr）或ST抗原（neunac α2- 3galnac α1- 3galnac α1- ser /Thr）的MUC1未表现出自相互作用。然而，在ST-MUC1的情况下，在随后的神经氨酸酶和β-半乳糖苷酶治疗后观察到自相互作用。这种酶处理有望引入n-表位，这些观察结果进一步加强了观察到的相互作用是由GalNAc基团介导的结论。
The molecular mechanism(s) underlying the enhanced self-interactions of mucins possessing the Tn (GalNAcα1-Ser/Thr) or STn (NeuNAcα2-6GalNAcα1-Ser/Thr) cancer markers were investigated using optical tweezers (OT). The mucins examined included modified porcine submaxillary mucin containing the Tn epitope (Tn-PSM), ovine submaxillary mucin with the STn epitope (STn-OSM), and recombinant MUC1 analogs with either the Tn and STn epitope. OT experiments in which the mucins were immobilized onto polystyrene beads revealed identical self-interaction characteristics for all mucins. Identical binding strength and energy landscape characteristics were also observed for synthetic polymers displaying multiple GalNAc decorations. Polystyrene beads without immobilized mucins showed no self-interactions and also no interactions with mucin-decorated polystyrene beads. Taken together, the experimental data suggest that in these molecules, the GalNAc residue mediates interactions independent of the anchoring polymer backbone. Furthermore, GalNAc–GalNAc interactions appear to be responsible for self-interactions of mucins decorated with the STn epitope. Hence, Tn-MUC1 and STn-MUC1 undergo self-interactions mediated by the GalNAc residue in both epitopes, suggesting a possible molecular role in cancer. MUC1 possessing the T (Galβ1-3GalNAcα1-Ser/Thr) or ST antigen (NeuNAcα2-3Galβ1-3GalNAcα1-Ser/Thr) failed to show self-interactions. However, in the case of ST-MUC1, self-interactions were observed after subsequent treatment with neuraminidase and β-galactosidase. This enzymatic treatment is expected to introduce Tn-epitopes and these observations thus further strengthen the conclusion that the observed interactions are mediated by the GalNAc groups.