Abstract
Ferroptosis is a recently recognized form of non-apoptotic regulated cell death and usually driven by iron-dependent lipid peroxidation and has arisen to play a significant role in cancer biology. Distinct from other types of cell death in morphology, genetics, and biochemistry, ferroptosis is characterized by the accumulation of lipid peroxides and lethal reactive oxygen species controlled by integrated oxidant and antioxidant systems. Increasing evidence indicates that a variety of biological processes, including amino acid, iron, lactate, and lipid metabolism, as well as glutathione, phospholipids, NADPH, and coenzyme Q10 biosynthesis, are closely related to ferroptosis sensitivity. Abnormal ferroptotic response may modulate cancer progression by reprogramming the tumor microenvironment (TME). The TME is widely associated with tumor occurrence because it is the carrier of tumor cells, which interacts with surrounding cells through the circulatory and the lymphatic system, thus influencing the development and progression of cancer. Furthermore, the metabolism processes play roles in maintaining the homeostasis and evolution of the TME. Here, this review focuses on the ferroptosis-mediated crosstalk in the TME, as well as discussing the novel therapeutic strategies for cancer treatment.
Highlights
Iron is the most abundant element, by mass, in the Earth (Frey and Reed, 2012), and it is required in a variety of important biological processes in the human body, such as oxygen transport, DNA biosynthesis, adenosine triphosphate (ATP) synthesis, etc. (Bogdan et al, 2016)
Ferroptosis is a reactive oxygen species (ROS)-dependent form of cell death associated with the accumulation of excessive iron and lipid peroxidation, as well as changes in specific genes involved in regulating iron homeostasis and lipid peroxidation metabolism (Yan et al, 2021)
high mobility group box1 (HMGB1) released by ferroptotic cancer cells is a prototypical damage-associated molecular patterns (DAMPs) involved in the immunogenicity of cancer cells, and it triggers an inflammatory response in macrophages through binding to advanced glycosylation end-product-specific receptor (AGER/RAGE) (Wen et al, 2019)
Summary
Iron is the most abundant element, by mass, in the Earth (Frey and Reed, 2012), and it is required in a variety of important biological processes in the human body, such as oxygen transport, DNA biosynthesis, adenosine triphosphate (ATP) synthesis, etc. (Bogdan et al, 2016). Recent evidence indicated that ferroptotic cancer cells could release signal molecules, including oxidized lipid mediators, eicosanoids, and high mobility group box (HMGB1) (Friedmann Angeli et al, 2014; Kagan et al, 2017; Wen et al, 2019), into the ECM to modulate the anti-cancer immunity. These findings suggested the potential roles of TME in regulating ferroptosis, and the ferroptosis of cancer cells could affect the TME in turn. We aimed to discuss the emerging regulatory network between ferroptosis and TME in cancer cells and its potential role in cancer treatment
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