糖组学在乳腺癌中的研究进展

Progress of Glycomics in Breast Cancer

乳腺癌仍是备受关注的世界性健康问题,在女性人群中有较高的发病率和致死率.蛋白质的糖基化修饰是一种重要的翻译后修饰,糖基化的改变已被证明与生物学过程密切相关.异常表达的糖链是肿瘤细胞的主要特征之一,对肿瘤的发生、发展,特别是癌细胞的浸润、转移起重要作用.本文从参与调节肿瘤细胞代谢,破坏细胞间黏着,在循环系统中维持肿瘤细胞活性、增强癌细胞与血管内皮细胞黏着及促进血管生成等方面系统阐述了O-连接型N-乙酰葡糖胺、唾液酸化的Lewis抗原、黏蛋白型O-聚糖及包含多聚N-乙酰乳糖胺的β1-6GlcNAc分支型N-糖链等几种异常表达糖链在肿瘤细胞浸润、转移过程中的作用.最后,本文从糖组学角度讨论了与肿瘤相关的异常表达的糖链、糖蛋白、糖基转移酶及针对糖抗原的抗体在乳腺癌临床中的应用前景.

Breast cancer remains a public-health issue on a global scale. Although mammographic screening and molecular-based classification have been applied to the clinical treatment effectively, breast cancer still has high incidence and mortality in women. Therefore, the discovery of novel biomarkers and molecular targets for early diagnosis and treatment is still essential. Glycosylation is the enzymatic addition of sugars, or oligosaccharides, to proteins and lipids. This increases the diversity of the proteome and lipidome to a level unmatched by any other post-translational modification due to the various aspects of the molecule that can be modified, including the glycosidic bond and glycan composition, structure, and length. Altered glycosylation, a predominant feature of tumor cells, plays an important role in the pathogenesis and progression of various malignancies. This review describes the variety of glycosylation processes, such as O-GlcNAcylation, sialyl-Lewis antigen, mucin type O-linked glycosylation, and J31-6 GlcNAc-branched N-glycans with poly-LacNAc structure, involved in breast carcinogenesis, their effects in the regulation of metabolism, cell-cell adhesion of tumor cells, and preservation of tumor cell activity in the circulatory system, as well as promotion of angiogenesis of tumor tissue. Finally, the application referred to glycosylation, glycoproteins, glycan genes, enzymes, and anti-carbohydrate antibodies in the clinical management of patients with breast cancer is also discussed.