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Nature:FBP1酶——肾癌恶化的拦路虎,伏枫网-小川亚纱美,日本三级片,日本小川亚纱美极品a级片

2015-01-12伏枫网-小川亚纱美,日本三级片,日本小川亚纱美极品a级片16:40伏枫网-小川亚纱美,日本三级片,日本小川亚纱美极品a级片来源:网络整理伏枫网-小川亚纱美,日本三级片,日本小川亚纱美极品a级片伏枫网-小川亚纱美,日本三级片,日本小川亚纱美极品a级片

伏枫网-小川亚纱美,日本三级片,日本小川亚纱美极品a级片 基因治疗 Nature:FBP1酶——肾癌恶化的拦路虎

Nature:FBP1酶——肾癌恶化的拦路虎

来源:生物谷 2014-07-24 09:35

Nature:FBP1酶——肾癌恶化的拦路虎

2014年7月24日 讯 /生物谷BIOON/ --近日,来自宾夕法尼亚大学佩雷尔曼医学院的研究人员通过研究鉴别出了一种名为FBP1的酶类可以有效阻断肾癌的发展,这种酶类对于调节机体代谢非常关键,它们可以与特殊肾脏细胞的细胞核中的转录因子结合,并且抑制细胞的能量代谢,相关研究成果刊登于国际杂志Nature上。

研究者表示,这种名为FBP1的酶类或许在所有的肾脏肿瘤组织中都是缺失的,而缺失FBP1时的肿瘤细胞会高速产生能量,当FBP1正常发挥功能时失控的肿瘤细胞便会被抑制。肾透明细胞癌(ccRCC)是一种常见的肾癌,主要表现为肾癌细胞的糖原水平升高以及脂肪积累,过量储存的脂质会引发脂滴积累。

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为了揭示酶类FBP1的表观遗传学特性,研究小组对600多种肿瘤组织进行了代谢酶类的研究分析,发现FBP1在所有的肾癌组织中都出现了缺失,而在正常细胞的细胞质中却可以发现FBP1的表达,在缺失FBP1的细胞中研究者观察到了瓦博格效应(Warburg effect),即在有氧条件下肿瘤细胞仍主要利用糖酵解来供能,这将导致肿瘤细胞的过度生长,并且使其产生能量的速度是非癌性细胞的200多倍。

FBP1的独特双重功能或许可以帮助解释其为何在ccRCC中普遍存在缺失的现象,FBP1的缺失机制或许可以应用于研究人类癌症发病的根源;下一步研究人员将会通过鉴别机体的其它代谢路径,来测定肾癌细胞和肝癌细胞中代谢产物的含量,从而确定FBP1酶类在疾病发生过程中所扮演的角色,并且为后期进行小鼠模型及临床前研究提供一定的科学依据。(生物谷Bioon.com)

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doi:10.1038/nature13557
PMC:,伏枫网-小川亚纱美,日本三级片,日本小川亚纱美极品a级片
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Fructose-1,6-bisphosphatase opposes renal carcinoma progression

Bo Li, Bo Qiu, David S. M. Lee, Zandra E. Walton, Joshua D. Ochocki, Lijoy K. Mathew, Anthony Mancuso, Terence P. F. Gade, Brian Keith, Itzhak Nissim & M. Celeste Simon

Clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer1, is characterized by elevated glycogen levels and fat deposition2. These consistent metabolic alterations are associated with normoxic stabilization of hypoxia-inducible factors (HIFs)3 secondary to von Hippel–Lindau (VHL) mutations that occur in over 90% of ccRCC tumours4. However, kidney-specific VHL deletion in mice fails to elicit ccRCC-specific metabolic phenotypes and tumour formation5, suggesting that additional mechanisms are essential. Recent large-scale sequencing analyses revealed the loss of several chromatin remodelling enzymes in a subset of ccRCC (these included polybromo-1, SET domain containing 2 and BRCA1-associated protein-1, among others)6, 7, 8, 9, indicating that epigenetic perturbations are probably important contributors to the natural history of this disease. Here we used an integrative approach comprising pan-metabolomic profiling and metabolic gene set analysis and determined that the gluconeogenic enzyme fructose-1,6-bisphosphatase 1 (FBP1)10 is uniformly depleted in over six hundred ccRCC tumours examined. Notably, the human FBP1 locus resides on chromosome 9q22, the loss of which is associated with poor prognosis for ccRCC patients11. Our data further indicate that FBP1 inhibits ccRCC progression through two distinct mechanisms. First, FBP1 antagonizes glycolytic flux in renal tubular epithelial cells, the presumptive ccRCC cell of origin12, thereby inhibiting a potential Warburg effect13, 14. Second, in pVHL (the protein encoded by the VHL gene)-deficient ccRCC cells, FBP1 restrains cell proliferation, glycolysis and the pentose phosphate pathway in a catalytic-activity-independent manner, by inhibiting nuclear HIF function via direct interaction with the HIF inhibitory domain. This unique dual function of the FBP1 protein explains its ubiquitous loss in ccRCC, distinguishing FBP1 from previously identified tumour suppressors that are not consistently mutated in all tumours6, 7, 15.

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