Ferroptosis in gastrointestinal cancer: from mechanisms to implications. (1st May 2023)

• Record Type: Journal Article
• Authors: Zhang, Ruoxi; Kang, Rui; Tang, Daolin
• Is Part Of: Cancer letters. Volume 561(2023)
• Publication Date: 2023-05-01
• Subjects: Gastrointestinal cancers -- lipid peroxidation -- GPX4 -- SLC7A11 -- autophagy -- regulated cell death; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2023.216147
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Ferroptosis is a form of regulated cell death that is initiated by excessive lipid peroxidation that results in plasma membrane damage and the release of damage-associated molecular patterns. In recent years, ferroptosis has gained significant attention in cancer research due to its unique mechanism compared to other forms of regulated cell death, especially caspase-dependent apoptotic cell death. Gastrointestinal (GI) cancer encompasses malignancies that arise in the digestive tract, including the stomach, intestines, pancreas, colon, liver, rectum, anus, and biliary system. These cancers are a global health concern, with high incidence and mortality rates. Despite advances in medical treatments, drug resistance caused by defects in apoptotic pathways remains a persistent challenge in the management of GI cancer. Hence, exploring the role of ferroptosis in GI cancers may lead to more efficacious treatment strategies. In this review, we provide a comprehensive overview of the core mechanism of ferroptosis and discuss its function, regulation, and implications in the context of GI cancers. Highlights: Ferroptosis is an iron-dependent cell death driven by excessive lipid peroxide accumulation on membranes. The major defense system of ferroptosis is the SLC7A11-GSH-GPX4 axis. Calcium-dependent ESCRT-III can repair membrane damage during ferroptosis. Ferroptosis has both pro-tumor and anti-tumor effects in GI cancers.