文章：

肿瘤中的糖基化：机制和临床意义

Glycosylation in cancer: mechanisms and clinical implications

原文发布日期：2015-08-20

DOI: 10.1038/nrc3982

类型: Review Article

开放获取: 否

要点：

1. Glycosylation is a key cellular mechanism regulating several physiological and pathological functions. Alterations in glycoproteins, glycosphingolipids and proteoglycans are common features of cancer cells.
2. The most-widely occurring cancer-associated changes in protein glycosylation are increased sialylation, increased branched-glycan structures and overexpression of 'core' fucosylation.
3. The overexpression of branched-N-glycan structures interferes with epithelial cadherin-mediated cell–cell adhesion, promoting tumour cell dissociation and invasion.
4. Modifications of integrins with branched N-glycans, truncated O-glycans and/or sialylated structures modulate tumour cell–matrix interactions, fostering the process of tumour cell migration.
5. Altered expression of proteoglycans and their glycosaminoglycan chains interfere with extracellular signalling molecules and modulate the activation of tyrosine kinase protein receptors.
6. Altered glycosylation of growth factor receptors and the modified expression of gangliosides affect cancer cell signal transduction pathways, modulating tumour cell growth and proliferation.
7. Glycans and their corresponding endogenous carbohydrate-recognition lectins are key regulators of the inflammation and immune response towards the tumour cells.
8. Several serological markers currently used in the clinic are based on the detection of circulating glycoproteins or glycoconjugates with altered glycosylation.
9. Glycans have major potential applications in improving early diagnosis, determination of prognosis and risk stratification, as well as in serving as markers of specific therapeutic targets.

要点翻译：

1. 糖基化是一种关键的细胞机制，调控多种生理和病理功能。糖蛋白、糖鞘脂和蛋白聚糖的改变是癌细胞的常见特征。
2. 蛋白质糖基化中最常见的癌症相关变化包括唾液酸化增强、支链聚糖结构增加以及"核心"岩藻糖基化的过度表达。
3. 支链N-聚糖结构的过度表达会干扰上皮钙黏蛋白介导的细胞间黏附，促进肿瘤细胞解离和侵袭。
4. 具有支链N-聚糖、截短O-聚糖和/或唾液酸化结构的整合素修饰会调节肿瘤细胞与基质的相互作用，促进肿瘤细胞迁移过程。
5. 蛋白聚糖及其糖胺聚糖链的表达改变会干扰细胞外信号分子，并调节酪氨酸激酶蛋白受体的激活。
6. 生长因子受体的糖基化改变和神经节苷脂的表达变化会影响癌细胞信号转导通路，从而调节肿瘤细胞的生长和增殖。
7. 聚糖及其对应的内源性碳水化合物识别凝集素是调节针对肿瘤细胞的炎症和免疫反应的关键因素。
8. 目前临床使用的几种血清学标志物基于检测具有异常糖基化的循环糖蛋白或糖缀合物。
9. 聚糖在改善早期诊断、确定预后和风险分层以及作为特定治疗靶点的标志物方面具有巨大的潜在应用价值。

英文摘要：

Despite recent progress in understanding the cancer genome, there is still a relative delay in understanding the full aspects of the glycome and glycoproteome of cancer. Glycobiology has been instrumental in relevant discoveries in various biological and medical fields, and has contributed to the deciphering of several human diseases. Glycans are involved in fundamental molecular and cell biology processes occurring in cancer, such as cell signalling and communication, tumour cell dissociation and invasion, cell–matrix interactions, tumour angiogenesis, immune modulation and metastasis formation. The roles of glycans in cancer have been highlighted by the fact that alterations in glycosylation regulate the development and progression of cancer, serving as important biomarkers and providing a set of specific targets for therapeutic intervention. This Review discusses the role of glycans in fundamental mechanisms controlling cancer development and progression, and their applications in oncology.

摘要翻译： 

尽管在理解癌症基因组方面近期已取得进展，但对癌症糖组与糖蛋白质组全貌的认知仍相对滞后。糖生物学推动了生物学与医学多领域的重大发现，并助力解析多种人类疾病。聚糖参与癌症中细胞信号传导、细胞间通讯、肿瘤细胞解离与侵袭、细胞-基质相互作用、肿瘤血管生成、免疫调节及转移形成等核心分子与细胞生物学过程。聚糖在癌症中的作用因糖基化改变可调控癌症的发生与进展而成为重要生物标志物，并提供特异的治疗干预靶点。本综述探讨聚糖在调控癌症发生与进展的核心机制中的角色及其在肿瘤学中的应用。

原文链接：

Glycosylation in cancer: mechanisms and clinical implications