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癌症发展过程中关键糖酵解蛋白的上调

Up-regulation of Key Glycolysis Proteins in Cancer Development.

作者信息

Nowak Nicole, Kulma Anna, Gutowicz Jan

机构信息

Institute of Genetics and Microbiology, University of Wrocław, Przybyszewskiego 63/77, 51-148 Wrocław, Poland.

Department of Biotechnology, Wrocław University, 51-148 Wrocław, Poland.

出版信息

Open Life Sci. 2018 Dec 31;13:569-581. doi: 10.1515/biol-2018-0068. eCollection 2018 Jan.

Abstract

In rapid proliferating cancer cells, there is a need for fast ATP and lactate production, therefore cancer cells turn off oxidative phosphorylation and turn on the so called "Warburg effect". This regulating the expression of genes involved in glycolysis. According to many studies, glucose transporter 1, which supplies glucose to the cell, is the most abundantly expressed transporter in cancer cells. Hexokinase 2, is one of four hexokinase isoenzymes, is also another highly expressed enzyme in cancer cells and it functions to enhance the glycolytic rate. The up-regulation of these two proteins has been established as an important factor in promoting development and metastasis in many types of cancer. Furthermore, other enzymes involved in glycolysis pathway such as phosphoglucose isomerase and glyceraldehyde 3-phosphate dehydrogenase, exhibit additional functions in promoting tumor growth in a non-glycolytic way. This review demonstrates the pivotal role of GLUT1, HK2, PGI and GAPDH in cancer development. In particular, we look at how the multifunctional proteins, PGI and GAPDH, affect cancer cell survival. We also present various clinical cancer cases in terms of the overexpression of selected proteins, which may be considered as a therapeutic target.

摘要

在快速增殖的癌细胞中,需要快速产生三磷酸腺苷(ATP)和乳酸,因此癌细胞会关闭氧化磷酸化并开启所谓的“瓦博格效应”。这会调节参与糖酵解的基因的表达。根据许多研究,向细胞供应葡萄糖的葡萄糖转运蛋白1是癌细胞中表达最丰富的转运蛋白。己糖激酶2是四种己糖激酶同工酶之一,也是癌细胞中另一种高表达的酶,其作用是提高糖酵解速率。这两种蛋白质的上调已被确认为促进多种癌症发展和转移的重要因素。此外,糖酵解途径中涉及的其他酶,如磷酸葡萄糖异构酶和甘油醛-3-磷酸脱氢酶,以非糖酵解的方式在促进肿瘤生长方面发挥额外作用。本综述阐述了葡萄糖转运蛋白1、己糖激酶2、磷酸葡萄糖异构酶和甘油醛-3-磷酸脱氢酶在癌症发展中的关键作用。特别是,我们研究多功能蛋白磷酸葡萄糖异构酶和甘油醛-3-磷酸脱氢酶如何影响癌细胞的存活。我们还根据所选蛋白质的过表达介绍了各种临床癌症病例,这些蛋白质过表达可被视为治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff8d/7874691/413022203585/biol-13-569-g001.jpg

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