Munkley Jennifer
Centre for Cancer, Biosciences Institute, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK.
Cancers (Basel). 2022 Aug 31;14(17):4248. doi: 10.3390/cancers14174248.
The surface of every eukaryotic cell is coated in a thick layer of glycans that acts as a key interface with the extracellular environment. Cancer cells have a different 'glycan coat' to healthy cells and aberrant glycosylation is a universal feature of cancer cells linked to all of the cancer hallmarks. This means glycans hold huge potential for the development of new diagnostic and therapeutic strategies. One key change in tumour glycosylation is increased sialylation, both on -glycans and -glycans, which leads to a dense forest of sialylated structures covering the cell surface. This hypersialylation has far-reaching consequences for cancer cells, and sialylated glycans are fundamental in tumour growth, metastasis, immune evasion and drug resistance. The development of strategies to inhibit aberrant sialylation in cancer represents an important opportunity to develop new therapeutics. Here, I summarise recent advances to target aberrant sialylation in cancer, including the development of sialyltransferase inhibitors and strategies to inhibit Siglecs and Selectins, and discuss opportunities for the future.
每个真核细胞的表面都覆盖着一层厚厚的聚糖，它是与细胞外环境的关键界面。癌细胞与健康细胞具有不同的“聚糖外衣”，异常糖基化是癌细胞的一个普遍特征，与所有癌症标志相关。这意味着聚糖在新诊断和治疗策略的开发中具有巨大潜力。肿瘤糖基化的一个关键变化是唾液酸化增加，包括O-聚糖和N-聚糖，这导致细胞表面覆盖着密集的唾液酸化结构。这种过度唾液酸化对癌细胞有深远影响，唾液酸化聚糖在肿瘤生长、转移、免疫逃逸和耐药性中起着重要作用。开发抑制癌症中异常唾液酸化的策略是开发新疗法的一个重要机会。在这里，我总结了针对癌症中异常唾液酸化的最新进展，包括唾液酸转移酶抑制剂的开发以及抑制唾液酸结合免疫球蛋白样凝集素（Siglecs）和选择素（Selectins）的策略，并讨论了未来的机会。
