Ferroptosis and EMT: key targets for combating cancer progression and therapy resistance

Abstract

AbstractIron-dependent lipid peroxidation causes ferroptosis, a form of regulated cell death. Crucial steps in the formation of ferroptosis include the accumulation of ferrous ions (Fe2+) and lipid peroxidation, of which are controlled by glutathione peroxidase 4 (GPX4). Its crucial role in stopping the spread of cancer has been shown by numerous studies undertaken in the last ten years. Epithelial–mesenchymal transition (EMT) is the process by which epithelial cells acquire mesenchymal characteristics. EMT is connected to carcinogenesis, invasiveness, metastasis, and therapeutic resistance in cancer. It is controlled by a range of internal and external signals and changes the phenotype from epithelial to mesenchymal like. Studies have shown that mesenchymal cancer cells tend to be more ferroptotic than their epithelial counterparts. Drug-resistant cancer cells are more easily killed by inducers of ferroptosis when they undergo EMT. Therefore, understanding the interaction between ferroptosis and EMT will help identify novel cancer treatment targets. In-depth discussion is given to the regulation of ferroptosis, the potential application of EMT in the treatment of cancer, and the relationships between ferroptosis, EMT, and signaling pathways associated with tumors. Invasion, metastasis, and inflammation in cancer all include ferroptosis and EMT. The goal of this review is to provide suggestions for future research and practical guidance for applying ferroptosis and EMT in clinical practice.