Aberrant protein glycosylation in the colon adenoma-cancer sequence: Colorectal cancer mechanisms and clinical implications

IF 4.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-04-17 DOI:10.1016/j.bbadis.2025.167853

He Yingli , Yang Ping , Yan Jun , Zhu Xingwang

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引用次数: 0

Abstract

Colorectal cancer (CRC) is a leading contributor to global cancer-related morbidity and mortality. Glycosylation is a common post-translational protein modification. Aberrant protein glycosylation is a hallmark of cancer, affecting biological processes and driving malignant CRC phenotypes. Specifically, abnormal N-glycosylation manifests as structural alterations in high mannose, sialylated, and fucosylated structures, collectively promoting cancer stemness and invasiveness. Concurrently, O-GlcNAcylation facilitates tumorigenesis through metabolic reprogramming and oncogene activation. Dysregulated mucin-type O-glycans (e.g., Core-1/Core-3 imbalance) and elevated SLex/SLea antigen expression are significantly correlated with tumor adhesion, metastatic dissemination, and adverse clinical outcomes. Furthermore, protein glycosylation contributes to chemoresistance through anti-apoptotic mechanisms, aberrant signaling activation, and pro-angiogenic pathways. This review systematically examines the dynamic evolution of protein glycosylation during CRC progression from normal mucosa to adenoma to adenocarcinoma. It also evaluates the CRC diagnostic and therapeutic implications of glycoproteins and glycans. This review can provide a molecular understanding for advancing CRC diagnostics and treatment.

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异常蛋白糖基化在结肠腺瘤-癌症序列：结直肠癌机制和临床意义

结直肠癌（CRC）是全球癌症相关发病率和死亡率的主要贡献者。糖基化是一种常见的翻译后蛋白质修饰。异常蛋白糖基化是癌症的一个标志，影响生物过程并驱动恶性CRC表型。具体来说，异常的n -糖基化表现为高甘露糖、唾液化和聚焦结构的结构改变，共同促进癌症的干性和侵袭性。同时，o - glcn酰化通过代谢重编程和癌基因激活促进肿瘤发生。黏液型o -聚糖失调（如Core-1/Core-3失衡）和SLex/SLea抗原表达升高与肿瘤粘附、转移传播和不良临床结果显著相关。此外，蛋白糖基化通过抗凋亡机制、异常信号激活和促血管生成途径促进化学耐药。本文系统地研究了CRC从正常粘膜到腺瘤再到腺癌进展过程中蛋白糖基化的动态演变。它还评估了糖蛋白和聚糖对结直肠癌的诊断和治疗意义。本文综述可以为推进结直肠癌的诊断和治疗提供分子认识。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biochimica et biophysica acta. Molecular basis of disease 生物-生化与分子生物学

CiteScore

12.30

自引率

0.00%

发文量

218

审稿时长

32 days

期刊介绍： BBA Molecular Basis of Disease addresses the biochemistry and molecular genetics of disease processes and models of human disease. This journal covers aspects of aging, cancer, metabolic-, neurological-, and immunological-based disease. Manuscripts focused on using animal models to elucidate biochemical and mechanistic insight in each of these conditions, are particularly encouraged. Manuscripts should emphasize the underlying mechanisms of disease pathways and provide novel contributions to the understanding and/or treatment of these disorders. Highly descriptive and method development submissions may be declined without full review. The submission of uninvited reviews to BBA - Molecular Basis of Disease is strongly discouraged, and any such uninvited review should be accompanied by a coverletter outlining the compelling reasons why the review should be considered.