ROS signalling in the biology of cancer

• Published in: Seminars in cell & developmental biology 2018-08, Vol.80, p.50-64
• Main Authors: Moloney, Jennifer N., Cotter, Thomas G.
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Antioxidants - pharmacology; Cancer; DNA Damage - genetics; Humans; Neoplasms - drug therapy; Neoplasms - metabolism; Oxidative Stress - physiology; Reactive oxygen species (ROS); Reactive Oxygen Species - metabolism; Signal Transduction - drug effects; Signal Transduction - physiology; Signalling; Therapy
• ISSN: 1084-9521; 1096-3634
• DOI: 10.1016/j.semcdb.2017.05.023

[Display omitted] •Different types of tumour cells produce elevated levels of reactive oxygen species (ROS) compared to their normal counterparts.•Mitochondria and NADPH oxidases (NOX) are two major contributors of endogenous ROS in tumour cells.•The antioxidant capacity of tumour cells strives to scavenge excessive ROS while maintain pro-tumourigenic signalling and resistance to apoptosis.•Increased ROS levels can also activate anti-tumourigenic signalling resulting in oxidative stress induced-cancer cell death.•Specific modifications of ROS generation and antioxidant defences are identified as targets in cancer therapy. Increased reactive oxygen species (ROS) production has been detected in various cancers and has been shown to have several roles, for example, they can activate pro-tumourigenic signalling, enhance cell survival and proliferation, and drive DNA damage and genetic instability. Counterintuitively ROS can also promote anti-tumourigenic signalling, initiating oxidative stress-induced tumour cell death. Tumour cells express elevated levels of antioxidant proteins to detoxify elevated ROS levels, establish a redox balance, while maintaining pro-tumourigenic signalling and resistance to apoptosis. Tumour cells have an altered redox balance to that of their normal counterparts and this identifies ROS manipulation as a potential target for cancer therapies. This review discusses the generation and sources of ROS within tumour cells, the regulation of ROS by antioxidant defence systems, as well as the effect of elevated ROS production on their signalling targets in cancer. It also provides an insight into how pro- and anti-tumourigenic ROS signalling pathways could be manipulated in the treatment of cancer.