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细胞膜唾液酸组:唾液酸作为人类癌症治疗中的治疗靶点和耐药性调节剂

Cell Membrane Sialome: Sialic Acids as Therapeutic Targets and Regulators of Drug Resistance in Human Cancer Management.

作者信息

Jastrząb Patrycja, Narejko Karolina, Car Halina, Wielgat Przemyslaw

机构信息

Department of Clinical Pharmacology, Medical University of Bialystok, Waszyngtona 15A, 15-274 Bialystok, Poland.

Department of Experimental Pharmacology, Medical University of Bialystok, Szpitalna 37, 15-295 Bialystok, Poland.

出版信息

Cancers (Basel). 2023 Oct 22;15(20):5103. doi: 10.3390/cancers15205103.

Abstract

A cellular sialome is a physiologically active and dynamically changing component of the cell membrane. Sialylation plays a crucial role in tumor progression, and alterations in cellular sialylation patterns have been described as modulators of chemotherapy effectiveness. However, the precise mechanisms through which altered sialylation contributes to drug resistance in cancer are not yet fully understood. This review focuses on the intricate interplay between sialylation and cancer treatment. It presents the role of sialic acids in modulating cell-cell interactions, the extracellular matrix (ECM), and the immunosuppressive processes within the context of cancer. The issue of drug resistance is also discussed, and the mechanisms that involve transporters, the tumor microenvironment, and metabolism are analyzed. The review explores drugs and therapeutic approaches that may induce modifications in sialylation processes with a primary focus on their impact on sialyltransferases or sialidases. Despite advancements in cellular glycobiology and glycoengineering, an interdisciplinary effort is required to decipher and comprehend the biological characteristics and consequences of altered sialylation. Additionally, understanding the modulatory role of sialoglycans in drug sensitivity is crucial to applying this knowledge in clinical practice for the benefit of cancer patients.

摘要

细胞唾液酸组是细胞膜中具有生理活性且动态变化的组成部分。唾液酸化在肿瘤进展中起着关键作用,细胞唾液酸化模式的改变已被描述为化疗效果的调节因子。然而,唾液酸化改变导致癌症耐药的确切机制尚未完全阐明。本综述聚焦于唾液酸化与癌症治疗之间的复杂相互作用。它阐述了唾液酸在癌症背景下调节细胞间相互作用、细胞外基质(ECM)和免疫抑制过程中的作用。还讨论了耐药问题,并分析了涉及转运蛋白、肿瘤微环境和代谢的机制。本综述探讨了可能诱导唾液酸化过程发生改变的药物和治疗方法,主要关注它们对唾液酸转移酶或唾液酸酶的影响。尽管细胞糖生物学和糖工程取得了进展,但仍需要跨学科的努力来解读和理解唾液酸化改变的生物学特征及后果。此外,了解唾液酸聚糖在药物敏感性中的调节作用对于将这一知识应用于临床实践以造福癌症患者至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfaf/10604966/810dfeb571ba/cancers-15-05103-g001.jpg

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