The genetic basis of kidney cancer: a metabolic disease.
The genetic basis of kidney cancer: a metabolic disease.
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DOI：
10.1038/nrurol.2010.47
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发表时间：
2010-05
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影响因子：
--
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中科院分区：
文献类型：
--
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肾癌不是一种单一的疾病，而是包括发生在肾脏中的许多不同类型的癌症，每种癌症由不同的基因引起，具有不同的组织学和临床过程，对治疗的反应不同。七种已知的肾癌基因VHL、MET、FLCN、TSC 1、TSC 2、FH和SDH中的每一种都参与对代谢应激和/或营养刺激做出响应的途径。VHL蛋白是调节细胞中HIF水平的氧和铁传感途径的组分。HGF/MET信号传导影响LKB1/AMPK能量感应级联。FLCN/FNIP1/FNIP2复合物结合AMPK，因此可能与细胞能量和营养感测途径AMPK-TSC 1/2-mTOR和PI3K-Akt-mTOR相互作用。TSC1/TSC2位于AMPK的下游，并且响应于细胞能量不足而负调节mTOR。FH和SDH在线粒体三羧酸（TCA）循环中起核心作用，其活性通过氧化磷酸化与能量产生偶联。这些肾癌基因中的每一个中的突变导致参与氧、铁、能量和/或营养感测的代谢途径的失调，这表明肾癌是细胞代谢疾病。针对肾癌的基本代谢异常为开发针对该疾病的更有效形式的治疗提供了独特的机会。
Kidney cancer is not a single disease but encompasses a number of different types of cancer that occur in the kidney, each caused by a different gene with a different histology and clinical course that responds differently to therapy. Each of the seven known kidney cancer genes, VHL, MET, FLCN, TSC1, TSC2, FH and SDH, is involved in pathways that respond to metabolic stress and/or nutrient stimulation. The VHL protein is a component of the oxygen and iron sensing pathway that regulates HIF levels in the cell. HGF/MET signaling affects the LKB1/AMPK energy sensing cascade. The FLCN/FNIP1/FNIP2 complex binds AMPK and therefore may interact with the cellular energy and nutrient sensing pathways, AMPK-TSC1/2-mTOR and PI3K-Akt-mTOR. TSC1/TSC2 are downstream of AMPK and negatively regulate mTOR in response to cellular energy deficit. FH and SDH play a central role in the mitochondrial tricarboxylic acid (TCA) cycle whose activities are coupled to energy production through oxidative phosphorylation. Mutations in each of these kidney cancer genes result in dysregulation of metabolic pathways involved in oxygen, iron, energy and/or nutrient sensing suggesting that kidney cancer is a disease of cell metabolism. Targeting the fundamental metabolic abnormalities in kidney cancer provides a unique opportunity for the development of more effective forms of therapy for this disease.
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影响因子：
56.9
作者：
Jaakkola, P;Mole, DR;Ratcliffe, PJ
通讯作者：
Ratcliffe, PJ
DOI：
10.1073/pnas.93.20.10595
发表时间：
1996-10-01
影响因子：
11.1
作者：
Iliopoulos, O;Levy, AP;Goldberg, MA
通讯作者：
Goldberg, MA
影响因子：
3.5
作者：
CROSSEY, PA;MAHER, ER;FERGUSONSMITH, MA
通讯作者：
FERGUSONSMITH, MA
影响因子：
5.6
作者：
DAVIS, CJ;MOSTOFI, FK;SESTERHENN, IA
通讯作者：
SESTERHENN, IA
影响因子：
56.9
作者：
DUAN, DR;PAUSE, A;KLAUSNER, RD
通讯作者：
KLAUSNER, RD