Abstract:
An overview of the role of glycosylation in prostate cancer (PCa) development and progression is presented, focusing on recent advancements in defining the N-glycome through glycomic profiling and glycoproteomic methodologies. Glycosylation is a common post-translational modification typified by oligosaccharides attached N-linked to asparagine or O-linked to serine or threonine on carrier proteins. These attached sugars have crucial roles in protein folding and cellular recognition processes, such that altered glycosylation is a hallmark of cancer pathogenesis and progression. In the past decade, advancements in N-glycan profiling workflows using Matrix Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) technology have been applied to define the spatial distribution of glycans in PCa tissues. Multiple studies applying N-glycan MALDI-MSI to pathology-defined PCa tissues have identified significant alterations in N-glycan profiles associated with PCa progression. N-glycan compositions progressively increase in number, and structural complexity due to increased fucosylation and sialylation. Additionally, significant progress has been made in defining the glycan and glycopeptide compositions of prostatic-derived glycoproteins like prostate-specific antigen in tissues and biofluids. The glycosyltransferases involved in these changes are potential drug targets for PCa, and new approaches in this area are summarized. These advancements will be discussed in the context of the further development of clinical diagnostics and therapeutics targeting glycans and glycoproteins associated with PCa progression. Integration of large scale spatial glycomic data for PCa with other spatial-omic methodologies is now feasible at the tissue and single-cell levels.
摘要:
概述了糖基化在前列腺癌(PCa)发展和进展中的作用,重点介绍通过糖组学和糖蛋白质组学方法定义N-糖的最新进展。糖基化是一种常见的翻译后修饰,典型的是在载体蛋白上与天冬酰胺N-连接或与丝氨酸或苏氨酸O-连接的寡糖。这些附着的糖在蛋白质折叠和细胞识别过程中起着至关重要的作用,这样改变的糖基化是癌症发病机制和进展的标志。在过去的十年里,使用基质辅助激光解吸/电离质谱成像(MALDI-MSI)技术的N-聚糖分析工作流程的进步已用于定义PCa组织中聚糖的空间分布。将N-聚糖MALDI-MSI应用于病理定义的PCa组织的多项研究已经鉴定了与PCa进展相关的N-聚糖谱的显著改变。N-聚糖组合物数量逐渐增加,以及由于岩藻糖基化和唾液酸化增加而导致的结构复杂性。此外,在定义组织和生物流体中前列腺特异性抗原等前列腺衍生糖蛋白的聚糖和糖肽组成方面已经取得了重大进展。参与这些变化的糖基转移酶是PCa的潜在药物靶标,并总结了这方面的新方法。这些进展将在靶向与PCa进展相关的聚糖和糖蛋白的临床诊断和治疗的进一步发展的背景下进行讨论。现在,在组织和单细胞水平上,将PCa的大规模空间糖数据与其他空间组学方法整合是可行的。