Oxidative stress in obesity-associated hepatocellular carcinoma: sources, signaling and therapeutic challenges.

Oxidative stress in obesity-associated hepatocellular carcinoma: sources, signaling and therapeutic challenges.
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DOI:
10.1038/s41388-021-01950-y
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发表时间:
2021-08
期刊:
影响因子:
8
通讯作者:
Gurzov, Esteban N.
Gurzov, Esteban N.
中科院分区:
医学1区
文献类型:
--
作者:
Brahma, Manoja K.;Gilglioni, Eduardo H.;Zhou, Lang;Trepo, Eric;Chen, Pengyu;Gurzov, Esteban N.

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肥胖影响全球超过6.5亿人,是肝细胞癌(HCC)发展的公认风险因素。氧化应激可被认为是一种真正的肿瘤促进剂,有助于肝癌的发生和发展。事实上,HCC进展中涉及的关键事件之一是由脂肪酸流入和慢性炎症引起的活性氧(ROS)水平过高。本文综述了肥胖诱导的ROS的不同细胞内来源和肝肿瘤发生的分子机制。此外,我们强调最近的研究结果,指出BCL-2蛋白和蛋白酪氨酸磷酸酶(PTP)的活性失调的作用,在肝脏氧化应激和ROS介导的功能失调的信号,分别。最后,我们讨论了新的纳米技术策略的潜力和挑战,以防止在肥胖相关的肝细胞癌的ROS形成。
Obesity affects more than 650 million individuals worldwide and is a well-established risk factor for the development of hepatocellular carcinoma (HCC). Oxidative stress can be considered as a bona fide tumor promoter, contributing to the initiation and progression of liver cancer. Indeed, one of the key events involved in HCC progression is excessive levels of reactive oxygen species (ROS) resulting from the fatty acid influx and chronic inflammation. This review provides insights into the different intracellular sources of obesity-induced ROS and molecular mechanisms responsible for hepatic tumorigenesis. In addition, we highlight recent findings pointing to the role of the dysregulated activity of BCL-2 proteins and protein tyrosine phosphatases (PTPs) in the generation of hepatic oxidative stress and ROS-mediated dysfunctional signaling, respectively. Finally, we discuss the potential and challenges of novel nanotechnology strategies to prevent ROS formation in obesity-associated HCC.
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