贲门癌是一种常见的恶性肿瘤，近年来，贲门癌的发病率逐年上升，严重威胁人类健康。然而，人们对于贲门癌的发病机理知之甚少，这给早期诊断和有效治疗这种恶性肿瘤带来了困难。
近日，Molecular and Cellular Proteomics在线发表了中科院营养与代谢重点实验室谢东研究组对于贲门癌发生发展过程中糖代谢异常的最新研究结果。博士生蔡震和赵江沙等利用蛋白质组学、代谢组学、细胞和分子生物学方法，研究贲门癌中糖代谢相关的酶及代谢小分子的变化规律。他们发现，在贲门癌组织中，糖酵解和无氧呼吸的过程明显增强，而三羧酸循环以及氧化磷酸化过程被削弱。
进一步的细胞实验证明，乳酸脱氢酶和丙酮酸脱氢酶能够共同调控丙酮酸的走向，这种调控对肿瘤细胞的快速增殖至关重要。通过RNA干扰手段抑制乳酸脱氢酶表达或过表达丙酮酸脱氢酶，都能够促进更多的丙酮酸转变成为乙酰辅酶A而进入三羧酸循环，并降低肿瘤细胞的体外增殖能力和成瘤能力。
糖代谢通路中诸多代谢小分子的变化有可能成为未来贲门癌诊断的分子标记。此外，该研究也为治疗肿瘤提供了一条新思路，即干扰肿瘤细胞的代谢通路。乳酸脱氢酶和丙酮酸脱氢酶有可能成为贲门癌治疗研究的新靶点。
该工作得到了中国科学院、国家科技部、自然科学基金委及上海市科委的资助。（生物谷Bioon.com）
生物谷近期特别推荐会议：
2010细胞治疗研究进展与临床应用前沿研讨会 www.Cell-therapies.net 2010年9月23日-25日天津召开
第一届肿瘤基础和转化医学国际研讨会 www.cancerasia.org 2010年10月12日-10月15日上海召开
生物谷推荐原文出处：
Molecular and Cellular Proteomics doi: 10.1074/mcp.M110.000661
A combined proteomic and metabolomic profiling of gastric cardia cancer reveals characteristic dysregulations in glucose metabolism
Zhen Cai1, Jiang-Sha Zhao1, Jing-Jing Li1, Dan-ni Peng1, Xiao-Yan Wang2, Tian-Lu Chen2, Yun-Ping Qiu2, Ping-Ping Chen3, Wen-Jie Li3, Li-Yan Xu4, En-Ming Li4, Jason P.M. Tam5, Robert Z Qi5, Wei Jia2 and Dong Xie1,*
1 Institute for Nutritional Sciences, Chinese Academy of Sciences, China;
2 Shanghai Center for Systems Biomedicine, and School of Pharmacy, Shanghai Jiao Tong University, China;
3 College of Public Health, Zhengzhou University, China;
4 Department of Biochemistry and Molecular Biology, Medical College of Shantou University, China;
5 Department of Biochemistry, Hong Kong University of Sciences and Technology, China
Gastric cardia cancer (GCC) which occurs at the gastric-esophageal boundary is one of the most malignant tumors. In spite of its high mortality and morbidity, the molecular mechanism of initiation and progression of this disease is largely unknown. In this study, using proteomic and metabolomic approaches, we found that the level of several enzymes and their related metabolic intermediates involved in glucose metabolism are deregulated in GCC. Among these enzymes, two subunits controlling pyruvic acid efflux, lactate dehydrogenase A (LDHA) and pyruvate dehydrogenase B (PDHB), have been further analyzed in vitro. Either downregulation of lactate dehydrogenase (LDH) subunit LDHA, or overexpression of pyruvate dehydrogenase (PDH) subunit PDHB can force pyruvic acid into the Krebs cycle rather than glycolysis process in AGS cells, which inhibits cell growth and cell migration. Our results reflect an important glucose metabolic signature, especially, the dysregulation of pyruvic acid efflux in the development of GCC. Forced transition from glycolysis to the Krebs cycle has an inhibitory effect on GCC progression, providing potential therapeutic targets for this disease.
