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肿瘤-高尔基体:高尔基体碎片化是癌症进展的关键吗?

Onco-Golgi: Is Fragmentation a Gate to Cancer Progression?

作者信息

Petrosyan Armen

机构信息

Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.

出版信息

Biochem Mol Biol J. 2015;1(1). doi: 10.21767/2471-8084.100006. Epub 2015 Nov 7.

Abstract

The Golgi apparatus-complex is a highly dynamic organelle which is considered the "heart" of intracellular transportation. Since its discovery by Camillo Golgi in 1873, who described it as the "black reaction," and despite the enormous volume of publications about Golgi, this apparatus remains one of the most enigmatic of the cytoplasmic organelles. A typical mammalian Golgi consists of a parallel series of flattened, disk-shaped cisternae which align into stacks. The tremendous volume of Golgi-related incoming and outgoing traffic is mediated by different motor proteins, including members of the dynein, kinesin, and myosin families. Yet in spite of the strenuous work it performs, Golgi contrives to maintain its monolithic morphology and orchestration of matrix and residential proteins. However, in response to stress, alcohol, and treatment with many pharmacological drugs over time, Golgi undergoes a kind of disorganization which ranges from mild enlargement to critical scattering. While fragmentation of the Golgi was confirmed in cancer by electron microscopy almost fifty years ago, it is only in recent years that we have begun to understand the significance of Golgi fragmentation in the biology of tumors. Below author would like to focus on how Golgi fragmentation opens the doors for cascades of fatal pathways which may facilitate cancer progression and metastasis. Among the issues addressed will be the most important cancer-specific hallmarks of Golgi fragmentation, including aberrant glycosylation, abnormal expression of the Ras GTPases, dysregulation of kinases, and hyperactivity of myosin motor proteins.

摘要

高尔基体复合体是一种高度动态的细胞器,被认为是细胞内运输的“核心”。自1873年卡米洛·高尔基体发现它并将其描述为“黑色反应”以来,尽管关于高尔基体的出版物数量众多,但这个细胞器仍然是细胞质细胞器中最神秘的之一。典型的哺乳动物高尔基体由一系列平行排列的扁平盘状潴泡组成,这些潴泡排列成堆叠状。大量与高尔基体相关的进出物质运输是由不同的马达蛋白介导的,包括动力蛋白、驱动蛋白和肌球蛋白家族的成员。然而,尽管高尔基体承担着繁重的工作,但它仍设法保持其整体形态以及基质蛋白和驻留蛋白的有序排列。然而,随着时间的推移,在应激、酒精和许多药物治疗的情况下,高尔基体经历了一种从轻度肿大到严重分散的紊乱。虽然近五十年前通过电子显微镜在癌症中证实了高尔基体的碎片化,但直到近年来我们才开始理解高尔基体碎片化在肿瘤生物学中的意义。以下作者将重点关注高尔基体碎片化如何为一系列致命途径打开大门,这些途径可能促进癌症进展和转移。其中将探讨的问题包括高尔基体碎片化最重要的癌症特异性特征,包括异常糖基化、Ras GTP酶的异常表达、激酶失调以及肌球蛋白马达蛋白的过度活跃。

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