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首页> 外文期刊>The EMBO journal. >Nuclear ARRB1 induces pseudohypoxia and cellular metabolism reprogramming in prostate cancer
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Nuclear ARRB1 induces pseudohypoxia and cellular metabolism reprogramming in prostate cancer

机译：核ARRB1诱发pseudohypoxia和细胞在前列腺癌代谢重编程

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Tumour cells sustain their high proliferation rate through metabolic reprogramming, whereby cellular metabolism shifts from oxidative phosphorylation to aerobic glycolysis, even under normal oxygen levels. Hypoxia-inducible factor 1A (HIF1A) is a major regulator of this process, but its activation under normoxic conditions, termed pseudohypoxia, is not well documented. Here, using an integrative approach combining the first genome-wide mapping of chromatin binding for an endocytic adaptor, ARRB1, both in vitro and in vivo with gene expression profiling, we demonstrate that nuclear ARRB1 contributes to this metabolic shift in prostate cancer cells via regulation of HIF1A transcriptional activity under normoxic conditions through regulation of succinate dehydrogenase A (SDHA) and fumarate hydratase (FH) expression. ARRB1-induced pseudohypoxia may facilitate adaptation of cancer cells to growth in the harsh conditions that are frequently encountered within solid tumours. Our study is the first example of an endocytic adaptor protein regulating metabolic pathways. It implicates ARRB1 as a potential tumour promoter in prostate cancer and highlights the importance of metabolic alterations in prostate cancer. Synopsis Global chromatin occupancy- and gene expression data, together with 'pseudohypoxic' regulation of HIF1alpha stability establish a predominantly metabolic function of nuclear ARRB1 in prostate cancer. Unbiased, genome-wide occupancy map of nuclear ARRB1 Integrated expression data that highlight ARRB1-regulated gene networks Discovery of ARRB1 as novel metabolic and cell cycle control regulator Evidence for pseudohypoxic stabilisation of HIFA by ARRB1 Global chromatin occupancy- and gene expression data, together with 'pseudohypoxic' regulation of HIF1alpha stability establish a predominantly metabolic function of nuclear ARRB1 in prostate cancer.
机译：肿瘤细胞维持较高的扩散率通过代谢重编程,即细胞从氧化磷酸化代谢变化有氧糖酵解,即使在正常的氧气的水平。这个过程的主要监管机构,但它的在常氧条件下激活,称为pseudohypoxia,不是良好的文档记录。使用一个综合疗法结合第一全基因组染色质的映射绑定的内吞作用的适配器,ARRB1体外和我们体内基因表达分析,证明核ARRB1导致这在前列腺癌细胞通过代谢转变HIF1A转录活动的监管在常氧条件下通过调节琥珀酸脱氢酶(SDHA)和延胡索酸酯水合酶(FH)表达式。pseudohypoxia可能促进癌症的适应在严酷的条件下,细胞增长经常遇到在固体肿瘤。研究的内吞作用的第一个例子适配器蛋白质调节代谢途径。涉及ARRB1作为一个潜在的肿瘤促进剂在前列腺癌和突出的重要性前列腺癌的代谢变化。简介全球染色质入住率和基因表达数据,连同“pseudohypoxic”建立一个监管HIF1alpha稳定主要核ARRB1的代谢功能在前列腺癌。入住率核ARRB1集成的地图突出ARRB1-regulated表达数据基因网络的发现ARRB1小说代谢和细胞周期控制调节器HIFA pseudohypoxic稳定的证据全球染色质ARRB1入住率和基因表达数据,连同“pseudohypoxic”建立一个监管HIF1alpha稳定主要核ARRB1的代谢功能在前列腺癌。

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  • 1. PROSTATE CANCER GEN. [P] . 外国专利： ES2190925T3 . 2003-09-01

    机译：prostate cancer gen.

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