Cancer is a difficult-to-cure disease with high worldwide incidence and mortality, in large part due to drug resistance and disease relapse. Glycosylation, which is a common modification of cellular biomolecules, was discovered decades ago and has been of interest in cancer research due to its ability to influence cellular function and to promote carcinogenesis. A variety of glycosylation types and structures regulate the function of biomolecules and are potential targets for investigating and treating cancer. The link between glycosylation and carcinogenesis has been more recently revealed by the role of p53 in energy metabolism, including the p53 target gene alpha-L-fucosidase 1 (FUCA1), which plays an essential role in fucosylation. In this review, we summarize roles of glycan structures and glycosylation-related enzymes to cancer development. The interplay between glycosylation and tumor microenvironmental factors is also discussed, together with involvement of glycosylation in well-characterized cancer-promoting mechanisms, such as the epidermal growth factor receptor (EGFR), phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) and p53-mediated pathways. Glycan structures also modulate cell–matrix interactions, cell–cell adhesion as well as cell migration and settlement, dysfunction of which can contribute to cancer. Thus, further investigation of the mechanistic relationships among glycosylation, related enzymes and cancer progression may provide insights into potential novel cancer treatments.
癌症是一种难以治愈的疾病，在全球范围内具有高发病率和高死亡率，这在很大程度上归因于耐药性和疾病复发。糖基化作为细胞生物分子的常见修饰方式，早在数十年前已被发现，并因其能够影响细胞功能、促进癌变而成为癌症研究的重要方向。多种糖基化类型与结构可调控生物分子功能，是研究和治疗癌症的潜在靶点。近年来，通过p53在能量代谢中的作用（包括其靶基因α-L-岩藻糖苷酶1在岩藻糖基化中的关键功能），糖基化与癌变之间的关联机制得到进一步揭示。本综述系统总结了聚糖结构及糖基化相关酶在癌症发展中的作用，探讨了糖基化与肿瘤微环境因素的相互作用，并阐述了糖基化在表皮生长因子受体、磷脂酰肌醇-3-激酶/蛋白激酶B及p53介导通路等经典促癌机制中的参与机制。聚糖结构还能调控细胞-基质相互作用、细胞间黏附以及细胞迁移与定植，这些功能的失调均可促进癌症发展。因此，进一步探究糖基化、相关酶与癌症进展之间的机制关联，可能为开发新型癌症治疗方法提供重要思路。
FUCA1: An Underexplored p53 Target Gene Linking Glycosylation and Cancer Progression
肿瘤(癌症)患者之家