State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China; Department of Clinical Pharmaceutics, Guangxi Academy of Medical Sciences and the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, China.
State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
Prog Lipid Res. 2023 Jul;91:101241. doi: 10.1016/j.plipres.2023.101241. Epub 2023 Jul 29.
Glycosphingolipids (GSLs) are major amphiphilic glycolipids present on the surface of living cell membranes. They have important biological functions, including maintaining plasma membrane stability, regulating signal transduction, and mediating cell recognition and adhesion. Specific GSLs and related enzymes are abnormally expressed in many cancer diseases and affect the malignant characteristics of tumors. The regulatory roles of GSLs in signaling pathways suggest that they are involved in tumor pathogenesis. GSLs have therefore been widely studied as diagnostic markers of cancer diseases and important targets of immunotherapy. This review describes the tumor-related biological functions of GSLs and systematically introduces recent progress in using diverse GSLs and related enzymes to diagnose and treat tumor diseases. Development of drugs and biomarkers for personalized cancer therapy based on GSL structure is also discussed. These advances, combined with recent progress in the preparation of GSLs derivatives through synthetic biology technologies, suggest a strong future for the use of customized GSL libraries in treating human diseases.
糖脂(Glycosphingolipids,GSLs)是存在于活细胞膜表面的主要两亲性糖脂。它们具有重要的生物学功能,包括维持质膜稳定性、调节信号转导以及介导细胞识别和黏附。许多癌症疾病中存在特定的 GSLs 和相关酶的异常表达,影响肿瘤的恶性特征。GSLs 在信号通路中的调节作用表明它们参与了肿瘤的发病机制。因此,GSLs 已被广泛研究作为癌症疾病的诊断标志物和免疫治疗的重要靶点。本文描述了 GSLs 与肿瘤相关的生物学功能,并系统介绍了利用多种 GSLs 和相关酶来诊断和治疗肿瘤疾病的最新进展。还讨论了基于 GSL 结构开发用于个性化癌症治疗的药物和生物标志物的情况。这些进展,结合通过合成生物学技术制备 GSL 衍生物的最新进展,表明在治疗人类疾病中使用定制的 GSL 文库具有广阔的前景。