Lipid metabolic reprogramming and associated ferroptosis in osteosarcoma: From molecular mechanisms to potential targets
Osteosarcoma is a common bone tumor in adolescents, which is characterized by lipid metabolism disorders and plays a key role in tumorigenesis and disease progression. Ferroptosis is an iron-dependent form of programmed cell death associated with lipid peroxidation. This review provides an in-depth...
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| Language: | English |
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Elsevier
2025-04-01
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| Series: | Journal of Bone Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212137425000016 |
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| author | Zhiyang Yin Guanlu Shen Minjie Fan Pengfei Zheng |
| author_facet | Zhiyang Yin Guanlu Shen Minjie Fan Pengfei Zheng |
| author_sort | Zhiyang Yin |
| collection | DOAJ |
| description | Osteosarcoma is a common bone tumor in adolescents, which is characterized by lipid metabolism disorders and plays a key role in tumorigenesis and disease progression. Ferroptosis is an iron-dependent form of programmed cell death associated with lipid peroxidation. This review provides an in-depth analysis of the complex relationship between lipid metabolic reprogramming and associated ferroptosis in OS from the perspective of metabolic enzymes and metabolites. We discussed the molecular basis of lipid uptake, synthesis, storage, lipolysis, and the tumor microenvironment, as well as their significance in OS development. Key enzymes such as adenosine triphosphate-citrate lyase (ACLY), acetyl-CoA synthetase 2 (ACSS2), fatty acid synthase (FASN) and stearoyl-CoA desaturase-1 (SCD1) are overexpressed in OS and associated with poor prognosis.Based on specific changes in metabolic processes, this review highlights potential therapeutic targets in the lipid metabolism and ferroptosis pathways, and in particular the HMG-CoA reductase inhibitor simvastatin has shown potential in inducing apoptosis and inhibiting OS metastasis. Targeting these pathways provides new strategies for the treatment of OS. However, challenges such as the complexity of drug development and metabolic interactions must be overcome. A comprehensive understanding of the interplay between dysregulation of lipid metabolism and ferroptosis is essential for the development of innovative and effective therapies for OS, with the ultimate goal of improving patient outcomes. |
| format | Article |
| id | doaj-art-62bf34b4c5d240e8bd2e9798b5c22778 |
| institution | Kabale University |
| issn | 2212-1374 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Bone Oncology |
| spelling | doaj-art-62bf34b4c5d240e8bd2e9798b5c227782025-01-31T05:11:15ZengElsevierJournal of Bone Oncology2212-13742025-04-0151100660Lipid metabolic reprogramming and associated ferroptosis in osteosarcoma: From molecular mechanisms to potential targetsZhiyang Yin0Guanlu Shen1Minjie Fan2Pengfei Zheng3Department of Orthopaedics Surgery, Children’s Hospital of Nanjing Medical University, Nanjing 210000 Jiangsu Province, ChinaSchool of Pharmacy, Jiangsu Ocean University, Lianyungang, Jiangsu, ChinaDepartment of Orthopaedics Surgery, Children’s Hospital of Nanjing Medical University, Nanjing 210000 Jiangsu Province, ChinaDepartment of Orthopaedics Surgery, Children’s Hospital of Nanjing Medical University, Nanjing 210000 Jiangsu Province, China; Corresponding author.Osteosarcoma is a common bone tumor in adolescents, which is characterized by lipid metabolism disorders and plays a key role in tumorigenesis and disease progression. Ferroptosis is an iron-dependent form of programmed cell death associated with lipid peroxidation. This review provides an in-depth analysis of the complex relationship between lipid metabolic reprogramming and associated ferroptosis in OS from the perspective of metabolic enzymes and metabolites. We discussed the molecular basis of lipid uptake, synthesis, storage, lipolysis, and the tumor microenvironment, as well as their significance in OS development. Key enzymes such as adenosine triphosphate-citrate lyase (ACLY), acetyl-CoA synthetase 2 (ACSS2), fatty acid synthase (FASN) and stearoyl-CoA desaturase-1 (SCD1) are overexpressed in OS and associated with poor prognosis.Based on specific changes in metabolic processes, this review highlights potential therapeutic targets in the lipid metabolism and ferroptosis pathways, and in particular the HMG-CoA reductase inhibitor simvastatin has shown potential in inducing apoptosis and inhibiting OS metastasis. Targeting these pathways provides new strategies for the treatment of OS. However, challenges such as the complexity of drug development and metabolic interactions must be overcome. A comprehensive understanding of the interplay between dysregulation of lipid metabolism and ferroptosis is essential for the development of innovative and effective therapies for OS, with the ultimate goal of improving patient outcomes.http://www.sciencedirect.com/science/article/pii/S2212137425000016Lipid metabolic reprogrammingOsteosarcomaFerroptosisFatty acidCholesterol |
| spellingShingle | Zhiyang Yin Guanlu Shen Minjie Fan Pengfei Zheng Lipid metabolic reprogramming and associated ferroptosis in osteosarcoma: From molecular mechanisms to potential targets Journal of Bone Oncology Lipid metabolic reprogramming Osteosarcoma Ferroptosis Fatty acid Cholesterol |
| title | Lipid metabolic reprogramming and associated ferroptosis in osteosarcoma: From molecular mechanisms to potential targets |
| title_full | Lipid metabolic reprogramming and associated ferroptosis in osteosarcoma: From molecular mechanisms to potential targets |
| title_fullStr | Lipid metabolic reprogramming and associated ferroptosis in osteosarcoma: From molecular mechanisms to potential targets |
| title_full_unstemmed | Lipid metabolic reprogramming and associated ferroptosis in osteosarcoma: From molecular mechanisms to potential targets |
| title_short | Lipid metabolic reprogramming and associated ferroptosis in osteosarcoma: From molecular mechanisms to potential targets |
| title_sort | lipid metabolic reprogramming and associated ferroptosis in osteosarcoma from molecular mechanisms to potential targets |
| topic | Lipid metabolic reprogramming Osteosarcoma Ferroptosis Fatty acid Cholesterol |
| url | http://www.sciencedirect.com/science/article/pii/S2212137425000016 |
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