基于N-糖基化分析恶性肿瘤高表达甘露糖基的生物学意义

Biological significance of mannosyl high expression in malignant tumors based on N-glycosylation

甘露糖基化修饰是蛋白质糖基化的重要组成部分,在肺癌、乳腺癌、肝细胞癌、结直肠癌等多种恶性肿瘤细胞恶变过程中存在特征性甘露糖基高表达。本文通过对甘露糖在细胞内的代谢过程、N-糖基化的合成过程及高尔基体内糖基修饰相关过程的阐述,总结了异常N-糖基化与肿瘤之间的关系。在此基础上,通过对恶性肿瘤高表达高甘露糖型N-聚糖相关文献的分析,指出恶性肿瘤异常高甘露糖基化的原因是癌细胞生长速率过快、早分泌的高甘露糖型N-聚糖链堆积、高尔基体α-糖苷酶和糖基转移酶异常表达,并提出异常高甘露糖基化加速了癌细胞的恶性潜能,参与介导内皮细胞活化,促进肿瘤转移,与肿瘤细胞生长、黏附、侵袭相关联,且在调节免疫监察点的过程中发挥重要生物学作用。目前已有研究尝试利用这些特性开发治疗癌症的药物,因此,笔者提出恶性肿瘤细胞高表达的甘露糖基可作为肿瘤治疗的靶点,进一步研究甘露糖基参与恶性肿瘤发展的信号通路,明确其在免疫监视和引发抗肿瘤免疫中的作用机制,将发掘甘露糖基在肿瘤治疗中的潜在作用,为肿瘤治疗开辟一条新路径。

Mannosylation is an important part of protein glycosylation.There is characteristic high expression of mannosyl in the malignant transformation of a variety of malignant tumor cells,including lung cancer,breast cancer,hepatocellular carcinoma and colorectal cancer.This review briefly describes the metabolic process of mannose in cells,the synthesis process of N-glycosylation and the related process of glycosylation modification in Golgi.The relationship between abnormal N-glycosylation and tumor was summarized in this review.On this basis,through the analysis of the literature related to the high expression of mannosyl in malignant tumors,it is pointed out that the causes of abnormal high mannosylation in malignant tumors are the accumulation of early secreted high mannose N-glycan caused by too fast growth rate of cancer cells,and the abnormal expression of glycosidase and glycosyltransferase in the Golgi compartment.It is suggested that the high expression of mannose groups accelerates the malignant potential of cancer cells,participates in mediating the activation of endothelial cells,promotes tumor metastasis.It is associated with tumor cell growth,adhesion,invasion.It also plays an important biological role in regulating immune surveillance points.At present,studies have attempted to use these characteristics to develop drugs for the treatment of cancer.Therefore,the author proposes that the highly expressed mannosyl of tumor cells can be used as an important target for tumor therapy.By further studying the pathways of mannose in the development of malignant tumors,and clarifying its mechanism of action in immune surveillance and initiating anti-tumor immunity,the potential role of mannose in clinical treatment may be explored.