Poliakov Eugenia, Managadze David, Rogozin Igor B
Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
Genet Res Int. 2014;2014:646193. doi: 10.1155/2014/646193. Epub 2014 Aug 27.
More than half a century from postulated Warburg theory of cancer cells origin, a question of changed metabolism in cancer is again taking the central place. Generalized picture of cancer metabolism was replaced by analysis of signaling and oncogenes in each type of cancer for several decades. However, now empowered with wealth of knowledge about tumor suppressors, oncogenes, and signaling pathways, reprogramming of cellular metabolism (e.g., increased glycolysis to respiration ratio in cancer cells) reemerged as an important element of cancer progression. To analyze level of expression of various proteins including metabolic enzymes across various cancers we used dbEST and Unigene data. We delineated a list of genes that are overexpressed in different types of cancer. We also grouped overexpressed enzymes into KEGG pathways and analyzed adjacent pathways to describe enzymatic reactions that take place in cancer cells and to identify major players that are abundant in cancer protein machinery. Glycolysis/gluconeogenesis and oxidative phosphorylation are the most abundant pathways although several other pathways are enriched in genes from our list. Ubiquitously overexpressed genes could be marked as nonspecific cancer-associated genes when analyzing genes that are overexpressed in certain types of cancer. Thus the list of overexpressed genes may be a useful tool for cancer research.
自提出癌细胞起源的瓦尔堡理论已过去半个多世纪,癌症中代谢变化的问题再次占据核心地位。几十年来,癌症代谢的整体图景被对每种癌症类型中信号传导和癌基因的分析所取代。然而,如今凭借对肿瘤抑制因子、癌基因和信号通路的丰富知识,细胞代谢重编程(例如癌细胞中糖酵解与呼吸比率增加)重新成为癌症进展的一个重要因素。为了分析包括代谢酶在内的各种蛋白质在不同癌症中的表达水平,我们使用了dbEST和基因文库数据。我们列出了在不同类型癌症中过度表达的基因清单。我们还将过度表达的酶归类到京都基因与基因组百科全书(KEGG)通路中,并分析相邻通路,以描述癌细胞中发生的酶促反应,并识别在癌症蛋白质机制中大量存在的主要参与者。糖酵解/糖异生和氧化磷酸化是最丰富的通路,尽管我们清单中的基因还富集了其他几条通路。在分析某些类型癌症中过度表达的基因时,普遍过度表达的基因可被标记为非特异性癌症相关基因。因此,过度表达基因清单可能是癌症研究的一个有用工具。