Understanding the mechanistic regulation of ferroptosis in cancer: the gene matters |
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| Institution: | 1. The Institute of Molecular and Translational Medicine, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi''an Jiaotong University Health Science Center, Xi''an, Shaanxi 710061, China;2. Department of Thoracic Surgery, The First Affiliated Hospital of Xi''an Jiaotong University, Xi''an, Shaanxi 710061, China;3. Department of Obstetrics, Xi ''an New Chang ''an Maternity Hospital, Xi''an, Shaanxi 710001, China;4. Shaanxi Stem Cell Engineering Application Research Center, Shaanxi Jiuzhou Biomedical Science and Technology Group, Xi''an, Shaanxi 710065, China;1. Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA;2. Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN 46556, USA;3. Rush School of Medicine, Chicago, IL 60612, USA;1. Key Laboratory of Zoonosis Research, Ministry of Education, College of Animal Science, Jilin University, Changchun, Jilin 130062, China;2. CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, China;3. Guangzhou Regenerative Medicine and Health Guang Dong Laboratory (GRMH-GDL), Guangzhou, Guangdong 510005, China;4. Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China |
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| Abstract: | Ferroptosis has emerged as a crucial regulated cell death involved in a variety of physiological processes or pathological diseases, such as tumor suppression. Though initially being found from anticancer drug screening and considered not essential as apoptosis for growth and development, numerous studies have demonstrated that ferroptosis is tightly regulated by key genetic pathways and/or genes, including several tumor suppressors and oncogenes. In this review, we introduce the basic concepts of ferroptosis, characterized by the features of non-apoptotic, iron-dependent, and overwhelmed accumulation of lipid peroxides, and the underlying regulated circuits are considered to be pro-ferroptotic pathways. Then, we discuss several established lipid peroxidation defending systems within cells, including SLC7A11/GPX4, FSP1/CoQ, GCH1/BH4, and mitochondria DHODH/CoQ, all of which serve as anti-ferroptotic pathways to prevent ferroptosis. Moreover, we provide a comprehensive summary of the genetic regulation of ferroptosis via targeting the above-mentioned pro-ferroptotic or anti-ferroptotic pathways. The regulation of pro- and anti-ferroptotic pathways gives rise to more specific responses to the tumor cells in a context-dependent manner, highlighting the unceasing study and deeper understanding of mechanistic regulation of ferroptosis for the purpose of applying ferroptosis induction in cancer therapy. |
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| Keywords: | Ferroptosis Ferroptotic pathways Genetic regulation Tumor suppression Cancer therapy |
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