Microenvironmental control of glucose metabolism in tumors by regulation of pyruvate dehydrogenase.
Microenvironmental control of glucose metabolism in tumors by regulation of pyruvate dehydrogenase.
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DOI：
10.1002/ijc.31812
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发表时间：
2019-02-15
影响因子：
6.4
通讯作者：
Papandreou I
中科院分区：
文献类型：
--
作者：
Golias T;Kery M;Radenkovic S;Papandreou I
在恶性肿瘤的发展过程中，癌细胞经历了一系列的变化，这些变化促进了它们的生存、侵袭和转移过程。其中之一是葡萄糖代谢的变化。与主要依靠三羧酸循环（TCA）的正常细胞不同，许多癌症类型依赖于糖酵解。丙酮酸脱氢酶复合物（PDC）是这两种途径之间的看门酶，负责将丙酮酸转化为乙酰辅酶a，然后在TCA循环中进一步处理。其活性受丙酮酸脱氢酶（PDP）和丙酮酸脱氢酶激酶（PDHK）调控。丙酮酸脱氢酶激酶存在4种组织特异性亚型（PDHK1-4），其活性受激素、缺氧和营养等不同因素的调控。PDHK1和PDHK3在低氧肿瘤微环境中活跃，抑制PDC，导致线粒体功能下降，糖酵解途径激活。PDHK1/3高表达与患者预后差相关，这使其成为癌症治疗的一个有希望的靶点。然而，更好地了解PDC在体内的酶调节和PDHK介导的恶性进展机制对于设计更好的PDHK抑制剂和选择最有可能从这些抑制剂中获益的患者是必要的。
During malignant progression cancer cells undergo a series of changes, which promote their survival, invasiveness and metastatic process. One of them is a change in glucose metabolism. Unlike normal cells, which mostly rely on the tricarboxylic acid cycle (TCA), many cancer types rely on glycolysis. Pyruvate dehydrogenase complex (PDC) is the gatekeeper enzyme between these two pathways and is responsible for converting pyruvate to acetyl-CoA, which can then be processed further in the TCA cycle. Its activity is regulated by PDP (pyruvate dehydrogenase phosphatases) and PDHK (pyruvate dehydrogenase kinases). Pyruvate dehydrogenase kinase exists in 4 tissue specific isoforms (PDHK1–4), the activities of which are regulated by different factors, including hormones, hypoxia, and nutrients. PDHK1 and PDHK3 are active in the hypoxic tumor microenvironment and inhibit PDC, resulting in a decrease of mitochondrial function and activation of the glycolytic pathway. High PDHK1/3 expression is associated with worse prognosis in patients, which makes them a promising target for cancer therapy. However, a better understanding of PDC’s enzymatic regulation in vivo and of the mechanisms of PDHK-mediated malignant progression is necessary for the design of better PDHK inhibitors and the selection of patients most likely to benefit from such inhibitors.
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影响因子：
3.7
作者：
Crewe C;Kinter M;Szweda LI
通讯作者：
Szweda LI
影响因子：
50.3
作者：
Chae YC;Vaira V;Caino MC;Tang HY;Seo JH;Kossenkov AV;Ottobrini L;Martelli C;Lucignani G;Bertolini I;Locatelli M;Bryant KG;Ghosh JC;Lisanti S;Ku B;Bosari S;Languino LR;Speicher DW;Altieri DC
通讯作者：
Altieri DC
影响因子：
4.8
作者：
Caruso, M;Maitan, MA;Beguinot, F
通讯作者：
Beguinot, F
影响因子：
--
作者：
Dai, ZhiJian;Pan, Shenhua;Lin, Sen
通讯作者：
Lin, Sen
胃癌的蛋白质组学和代谢组学联合分析揭示了葡萄糖代谢的特征性失调
影响因子：
7
作者：
Cai, Zhen;Zhao, Jiang-Sha;Xie, Dong
通讯作者：
Xie, Dong