Signal Transduction and Metabolism Laboratory, Laboratoire de Gastroentérologie Expérimental et Endotools, Université libre de Bruxelles, Brussels, Belgium.
Materials Research and Education Center, Auburn University, Auburn, AL, 36849, United States.
Oncogene. 2021 Aug;40(33):5155-5167. doi: 10.1038/s41388-021-01950-y. Epub 2021 Jul 21.
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.
肥胖影响着全球超过 6.5 亿人，并且是肝细胞癌（HCC）发展的一个既定的危险因素。氧化应激可以被认为是一个真正的肿瘤促进剂，有助于肝癌的发生和发展。事实上，HCC 进展过程中的一个关键事件是由于脂肪酸流入和慢性炎症导致的活性氧（ROS）水平过高。这篇综述深入探讨了肥胖诱导的 ROS 的不同细胞内来源以及导致肝肿瘤发生的分子机制。此外，我们还强调了最近的发现，这些发现指出 BCL-2 蛋白和蛋白酪氨酸磷酸酶（PTPs）的失调活性分别在肝脏氧化应激的产生和 ROS 介导的功能障碍信号转导中发挥作用。最后，我们讨论了利用新型纳米技术策略预防肥胖相关 HCC 中 ROS 形成的潜力和挑战。
