賁門(mén)癌是一種常見(jiàn)的惡性腫瘤,，近年來(lái)，賁門(mén)癌的發(fā)病率逐年上升,，嚴(yán)重威脅人類(lèi)健康,。然而，人們對(duì)于賁門(mén)癌的發(fā)病機(jī)理知之甚少,，這給早期診斷和有效治療這種惡性腫瘤帶來(lái)了困難,。
近日，Molecular and Cellular Proteomics在線發(fā)表了中科院營(yíng)養(yǎng)與代謝重點(diǎn)實(shí)驗(yàn)室謝東研究組對(duì)于賁門(mén)癌發(fā)生發(fā)展過(guò)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(xì)胞和分子生物學(xué)方法，研究賁門(mén)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(mén)癌組織中，糖酵解和無(wú)氧呼吸的過(guò)程明顯增強(qiáng),，而三羧酸循環(huán)以及氧化磷酸化過(guò)程被削弱,。
進(jìn)一步的細(xì)胞實(shí)驗(yàn)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(duì)腫瘤細(xì)胞的快速增殖至關(guān)重要。通過(guò)RNA干擾手段抑制乳酸脫氫酶表達(dá)或過(guò)表達(dá)丙酮酸脫氫酶,，都能夠促進(jìn)更多的丙酮酸轉(zhuǎn)變成為乙酰輔酶A而進(jìn)入三羧酸循環(huán),，并降低腫瘤細(xì)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(lái)賁門(mén)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(xì)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(mén)癌治療研究的新靶點(diǎn),。
該工作得到了中國(guó)科學(xué)院、國(guó)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(huì)議：
2010細(xì)胞治療研究進(jìn)展與臨床應(yīng)用前沿研討會(huì) www.Cell-therapies.net 2010年9月23日-25日天津召開(kāi)
第一屆腫瘤基礎(chǔ)和轉(zhuǎn)化醫(yī)學(xué)國(guó)際研討會(huì) www.cancerasia.org 2010年10月12日-10月15日上海召開(kāi)
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.
