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结直肠癌中与异常糖基化相关的耐药性。

Drug resistance related to aberrant glycosylation in colorectal cancer.

作者信息

Very Ninon, Lefebvre Tony, El Yazidi-Belkoura Ikram

机构信息

Unité de Glycobiologie Structurale et Fonctionnelle, UGSF-UMR 8576 CNRS, Université de Lille, Lille 59000, France.

出版信息

Oncotarget. 2017 Nov 3;9(1):1380-1402. doi: 10.18632/oncotarget.22377. eCollection 2018 Jan 2.

Abstract

Colorectal cancer (CRC) is the fourth leading cause of cancer-related deaths in the world. Drug resistance of tumour cells remains the main challenge toward curative treatments efficiency. Several epidemiologic studies link emergence and recurrence of this cancer to metabolic disorders. Glycosylation that modifies more than 80% of human proteins is one of the most widepread nutrient-sensitive post-translational modifications. Aberrant glycosylation participates in the development and progression of cancer. Thus, some of these glycan changes like carbohydrate antigen CA 19-9 (sialyl Lewis a, sLea) or those found on carcinoembryonic antigen (CEA) are already used as clinical biomarkers to detect and monitor CRC. The current review highlights emerging evidences accumulated mainly during the last decade that establish the role played by altered glycosylations in CRC drug resistance mechanisms that induce resistance to apoptosis and activation of signaling pathways, alter drug absorption and metabolism, and led to stemness acquisition. Knowledge in this field of investigation could aid to the development of better therapeutic approaches with new predictive biomarkers and targets tied in with adapted diet.

摘要

结直肠癌(CRC)是全球癌症相关死亡的第四大主要原因。肿瘤细胞的耐药性仍然是影响治疗效果的主要挑战。多项流行病学研究将这种癌症的发生和复发与代谢紊乱联系起来。糖基化修饰超过80%的人类蛋白质,是最广泛存在的营养敏感型翻译后修饰之一。异常糖基化参与癌症的发生和发展。因此,这些聚糖变化中的一些,如碳水化合物抗原CA 19-9(唾液酸化路易斯a,sLea)或癌胚抗原(CEA)上发现的那些聚糖变化,已被用作检测和监测CRC的临床生物标志物。本综述重点介绍了主要在过去十年中积累的新证据,这些证据确立了糖基化改变在CRC耐药机制中所起的作用,这些机制包括诱导对凋亡的抗性和信号通路的激活、改变药物吸收和代谢以及导致干性获得。该研究领域的知识有助于开发更好的治疗方法,以及与适应性饮食相关的新的预测生物标志物和靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d9b/5787446/be17e5f89799/oncotarget-09-1380-g001.jpg

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