賁門癌是一種常見的惡性腫瘤，近年來,，賁門癌的發(fā)病率逐年上升,，嚴(yán)重威脅人類健康。然而,，人們對于賁門癌的發(fā)病機理知之甚少,，這給早期診斷和有效治療這種惡性腫瘤帶來了困難。
近日,，Molecular and Cellular Proteomics在線發(fā)表了中科院營養(yǎng)與代謝重點實驗室謝東研究組對于賁門癌發(fā)生發(fā)展過程中糖代謝異常的最新研究結(jié)果。博士生蔡震和趙江沙等利用蛋白質(zhì)組學(xué),、代謝組學(xué),、細胞和分子生物學(xué)方法，研究賁門癌中糖代謝相關(guān)的酶及代謝小分子的變化規(guī)律,。他們發(fā)現(xiàn),，在賁門癌組織中，糖酵解和無氧呼吸的過程明顯增強,，而三羧酸循環(huán)以及氧化磷酸化過程被削弱,。
進一步的細胞實驗證明，乳酸脫氫酶和丙酮酸脫氫酶能夠共同調(diào)控丙酮酸的走向,，這種調(diào)控對腫瘤細胞的快速增殖至關(guān)重要,。通過RNA干擾手段抑制乳酸脫氫酶表達或過表達丙酮酸脫氫酶，都能夠促進更多的丙酮酸轉(zhuǎn)變成為乙酰輔酶A而進入三羧酸循環(huán),，并降低腫瘤細胞的體外增殖能力和成瘤能力,。
糖代謝通路中諸多代謝小分子的變化有可能成為未來賁門癌診斷的分子標(biāo)記。此外,，該研究也為治療腫瘤提供了一條新思路,，即干擾腫瘤細胞的代謝通路。乳酸脫氫酶和丙酮酸脫氫酶有可能成為賁門癌治療研究的新靶點,。
該工作得到了中國科學(xué)院,、國家科技部、自然科學(xué)基金委及上海市科委的資助,。（生物谷Bioon.com）
生物谷近期特別推薦會議：
2010細胞治療研究進展與臨床應(yīng)用前沿研討會 www.Cell-therapies.net 2010年9月23日-25日天津召開
第一屆腫瘤基礎(chǔ)和轉(zhuǎn)化醫(yī)學(xué)國際研討會 www.cancerasia.org 2010年10月12日-10月15日上海召開
生物谷推薦原文出處：
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.
