Open AccessOxidative stress in obesity-associated hepatocellular carcinoma: sources, signaling and therapeutic challenges
Author(s) -
Manoja K. Brahma,
Eduardo Hideo Gilglioni,
Lang Zhou,
Eric Trépo,
Pengyu Chen,
Esteban Nicolas Gurzov
Publication year - 2021
Publication title -
oncogene
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.395
H-Index - 342
eISSN - 1476-5594
pISSN - 0950-9232
DOI - 10.1038/s41388-021-01950-y
Subject(s) - oxidative stress , hepatocellular carcinoma , biology , carcinogenesis , reactive oxygen species , cancer research , inflammation , fatty liver , cancer , liver cancer , oxidative phosphorylation , bioinformatics , endocrinology , medicine , microbiology and biotechnology , immunology , biochemistry , genetics , disease
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.