Proteomic analysis of colorectal cancer reveals alterations in metabolic pathways - Mechanism of tumorigenesis
Proteomic analysis of colorectal cancer reveals alterations in metabolic pathways - Mechanism of tumorigenesis
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DOI：
10.1074/mcp.m500432-mcp200
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发表时间：
2006-06-01
影响因子：
7
通讯作者：
Hew, Choy-Leong
中科院分区：
文献类型：
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作者：
Bi, Xuezhi;Lin, Qingsong;Hew, Choy-Leong
结直肠癌是全球第二大杀手癌症，目前是新加坡男性中最常见的癌症。该研究旨在检测与结直肠肿瘤发生过程相关的蛋白质谱变化，以确定早期结直肠癌检测和诊断的特异性蛋白质标志物或作为潜在的治疗靶点。应用双向凝胶电泳技术，在碱性pH范围内（pH 7-10）对7对大肠癌组织及癌旁正常粘膜进行了检测。检测到34个点的强度变化具有统计学意义。通过MALDI-TOF/TOF串联质谱鉴定了34个斑点中的16个。蛋白质表达水平的变化揭示了糖酵解途径的显著增强（瓦尔堡效应）、糖异生减少、葡萄糖醛酸途径受抑制和三羧酸循环受损。通过二维DIGE验证了观察到的蛋白质丰度变化。这些变化揭示了结直肠肿瘤发生的潜在机制，其中受损的三羧酸循环和瓦尔堡效应的作用可能是至关重要的。
Colorectal cancer is the second leading killer cancer worldwide and presently the most common cancer among males in Singapore. The study aimed to detect changes of protein profiles associated with the process of colorectal tumorigenesis to identify specific protein markers for early colorectal cancer detection and diagnosis or as potential therapeutic targets. Seven pairs of colorectal cancer tissues and adjacent normal mucosa were examined by two-dimensional gel electrophoresis at basic pH range (pH 7-10). Intensity changes of 34 spots were detected with statistical significance. 16 of the 34 spots were identified by MALDI-TOF/TOF tandem mass spectrometry. Changes in protein expression levels revealed a significantly enhanced glycolytic pathway (Warburg effect), a decreased gluconeogenesis, a suppressed glucuronic acid pathway, and an impaired tricarboxylic acid cycle. Observed changes in protein abundance were verified by two-dimensional DIGE. These changes reveal an underlying mechanism of colorectal tumorigenesis in which the roles of impaired tricarboxylic acid cycle and the Warburg effect may be critical.