Heat shock transcription factor 1 is a key determinant of HCC development by regulating hepatic steatosis and metabolic syndrome.

Jin X; Moskophidis D; Mivechi NF

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Heat shock transcription factor 1 is a key determinant of HCC development by regulating hepatic steatosis and metabolic syndrome.

机译：通过调节肝脂肪变性和代谢综合征，热休克转录因子1是肝癌发展的关键决定因素。

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Hepatocellular carcinoma (HCC) occurrence and progression are linked tightly to progressive hepatic metabolic syndrome associated with insulin resistance, hepatic steatosis, and chronic inflammation. Heat shock transcription factor 1 (HSF1), a major transactivator of stress proteins, increases survival by protecting cells against environmental stressors. It has been implicated in the pathogenesis of cancer, but specific mechanisms by which HSF1 supports cancer development remain elusive. We propose a pathogenic mechanism whereby HSF1 activation promotes growth of premalignant cells and HCC development by stimulating lipid biosynthesis and perpetuating chronic hepatic metabolic disease induced by carcinogens. Our work shows that inactivation of HSF1 impairs cancer progression, mitigating adverse effects of carcinogens on hepatic metabolism by enhancing insulin sensitivity and sensitizing activation of AMP-activated protein kinase (AMPK), an important regulator of energy homeostasis and inhibitor of lipid synthesis. HSF1 is a potential target for the control of hepatic steatosis, hepatic insulin resistance, and HCC development.

机译：肝细胞癌（HCC）的发生和发展与与胰岛素抵抗，肝脂肪变性和慢性炎症相关的进行性肝代谢综合征紧密相关。热激转录因子1（HSF1）是应激蛋白的主要反式激活因子，可通过保护细胞免受环境应激因素的影响而提高存活率。它与癌症的发病机制有关，但是HSF1支持癌症发展的具体机制仍然难以捉摸。我们提出了一种致病机制，其中HSF1激活通过刺激脂质生物合成和使致癌物诱导的慢性肝代谢疾病永久性，从而促进癌前细胞的生长和肝癌的发展。我们的工作表明，HSF1失活可通过增强胰岛素敏感性和敏化AMP活化蛋白激酶（AMPK）（能量稳态和调节脂质合成的重要调节剂）的活化作用来削弱癌症进展，减轻致癌物对肝代谢的不良影响。 HSF1是控制肝脂肪变性，肝胰岛素抵抗和HCC发育的潜在靶标。

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《Cell metabolism》 |2011年第1期|共13页
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Jin X; Moskophidis D; Mivechi NF;
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中图分类内分泌腺疾病及代谢病;
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1. Heat shock transcription factor 1 is a key determinant of HCC development by regulating hepatic steatosis and metabolic syndrome. [J] . Jin X, Moskophidis D, Mivechi NF Cell metabolism . 2011,第1期

机译：通过调节肝脂肪变性和代谢综合征，热休克转录因子1是肝癌发展的关键决定因素。
2. Developmentally regulated nuclear transport of transcription factors in Drosophila embryos enable the heat shock response. [J] . Wang Z, Lindquist S Development . 1998,第23期

机译：果蝇胚胎中转录因子的发育调控核转运可实现热休克反应。
3. Arabidopsis HEAT SHOCK TRANSCRIPTION FACTORA1b regulates multiple developmental genes under benign and stress conditions [J] . Waleed SAlbihlal, ObomighieIrabonosi, ThomasBlein, Journal of Experimental Botany . 2018,第11期

机译：拟南芥热休克转录因子1b在良性和压力条件下调节多种发育基因
4. Mining Heat Stress Induced Genes Encoding Heat Shock Proteins (HSPs) and Heat Stress Transcription Factors (HSFs) in Strawberry (Fragaria x ananassa) [C] . Lee-Fong Lin, Shih-Yi Liao, Jui-Hung Yen, International Conference on Mechanics and Control Engineering . 2014

机译：采矿热应激诱导在草莓（Fragaria x ananassa）中编码热休克蛋白（HSP）和热应激转录因子（HSF）的热应激诱导基因
5. Two kinases negatively regulate the activity of the heat shock transcription factor in Saccharomyces cerevisiae [D] . Achenbach, Sara Elizabeth 2008

机译：两种激酶负调控酿酒酵母中热激转录因子的活性
6. Heat shock transcription factor 1 is a key determinant of HCC development by regulating hepatic steatosis and metabolic syndrome [O] . Xiongjie Jin, Demetrius Moskophidis, Nahid F. Mivechi -1

机译：热休克转录因子1是HCC的发展的关键因素是通过调节肝脂肪变性和代谢综合征
7. Heat Shock Transcription Factor 1 Is a Key Determinant of HCC Development by Regulating Hepatic Steatosis and Metabolic Syndrome [O] . Jin Xiongjie, Moskophidis Demetrius, Mivechi Nahid F. 2011

机译：通过调节肝脂肪变性和代谢综合征，热休克转录因子1是肝癌发展的关键决定因素。

Heat shock transcription factor 1 is a key determinant of HCC development by regulating hepatic steatosis and metabolic syndrome.

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