An Analysis of AMPK and Ferroptosis in Cancer: A Potential Regulatory Axis
Adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) is an energy homeostasis controller that regulates various metabolic pathways to promote adenosine triphosphate (ATP) generation and suppress energy expenditure, thereby restoring energy homeostasis. As a co-factor in many enzymes, iro...
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| Format: | Article |
| Language: | English |
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IMR Press
2025-07-01
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| Series: | Frontiers in Bioscience-Landmark |
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| Online Access: | https://www.imrpress.com/journal/FBL/30/7/10.31083/FBL36618 |
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| author | Ting Zhang Xi Wang Peter G Alexander Peng Feng Jianying Zhang |
| author_facet | Ting Zhang Xi Wang Peter G Alexander Peng Feng Jianying Zhang |
| author_sort | Ting Zhang |
| collection | DOAJ |
| description | Adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) is an energy homeostasis controller that regulates various metabolic pathways to promote adenosine triphosphate (ATP) generation and suppress energy expenditure, thereby restoring energy homeostasis. As a co-factor in many enzymes, iron is an essential mineral for maintaining ATP levels in our bodies. Ferroptosis is an iron-dependent mode of cell death that occurs in various pathological processes, including cancer, metabolic disorders, and autoimmune diseases, by regulating iron metabolism, lipoperoxidation, and anti-oxidation functions. Ferroptosis is triggered by oxidative and energy stress, both controlled by cancer-associated signaling pathways. Emerging studies have demonstrated that AMPK directly influences ferroptosis by modulating lipid metabolism, redox homeostasis, and iron transport. Cancer cells exhibiting elevated baseline AMPK activity demonstrate resistance to ferroptosis, whereas AMPK suppression enhances their susceptibility to this regulated form of cell death. While the precise mechanistic details are yet to be fully elucidated, accumulating evidence suggests that AMPK-mediated ferroptosis regulation may contribute to cancer development and therapeutic responses. This review summarizes recent advances in understanding the interplay between AMPK and ferroptosis in cancer biology and discusses the potential of targeting the AMPK-ferroptosis axis for innovative anticancer strategies. |
| format | Article |
| id | doaj-art-05a2b19ff15142099f1a4b4352f22dda |
| institution | Kabale University |
| issn | 2768-6701 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Frontiers in Bioscience-Landmark |
| spelling | doaj-art-05a2b19ff15142099f1a4b4352f22dda2025-08-20T04:02:13ZengIMR PressFrontiers in Bioscience-Landmark2768-67012025-07-013073661810.31083/FBL36618S2768-6701(25)01667-3An Analysis of AMPK and Ferroptosis in Cancer: A Potential Regulatory AxisTing Zhang0Xi Wang1Peter G Alexander2Peng Feng3Jianying Zhang4Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Trauma Orthopedics, The First Affiliated Hospital of Xinjiang Medical University, 830011 Urumqi, Xinjiang, ChinaDepartment of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USAAdenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) is an energy homeostasis controller that regulates various metabolic pathways to promote adenosine triphosphate (ATP) generation and suppress energy expenditure, thereby restoring energy homeostasis. As a co-factor in many enzymes, iron is an essential mineral for maintaining ATP levels in our bodies. Ferroptosis is an iron-dependent mode of cell death that occurs in various pathological processes, including cancer, metabolic disorders, and autoimmune diseases, by regulating iron metabolism, lipoperoxidation, and anti-oxidation functions. Ferroptosis is triggered by oxidative and energy stress, both controlled by cancer-associated signaling pathways. Emerging studies have demonstrated that AMPK directly influences ferroptosis by modulating lipid metabolism, redox homeostasis, and iron transport. Cancer cells exhibiting elevated baseline AMPK activity demonstrate resistance to ferroptosis, whereas AMPK suppression enhances their susceptibility to this regulated form of cell death. While the precise mechanistic details are yet to be fully elucidated, accumulating evidence suggests that AMPK-mediated ferroptosis regulation may contribute to cancer development and therapeutic responses. This review summarizes recent advances in understanding the interplay between AMPK and ferroptosis in cancer biology and discusses the potential of targeting the AMPK-ferroptosis axis for innovative anticancer strategies.https://www.imrpress.com/journal/FBL/30/7/10.31083/FBL36618ampkferroptosiscancerenergy metabolismiron homeostasis |
| spellingShingle | Ting Zhang Xi Wang Peter G Alexander Peng Feng Jianying Zhang An Analysis of AMPK and Ferroptosis in Cancer: A Potential Regulatory Axis Frontiers in Bioscience-Landmark ampk ferroptosis cancer energy metabolism iron homeostasis |
| title | An Analysis of AMPK and Ferroptosis in Cancer: A Potential Regulatory Axis |
| title_full | An Analysis of AMPK and Ferroptosis in Cancer: A Potential Regulatory Axis |
| title_fullStr | An Analysis of AMPK and Ferroptosis in Cancer: A Potential Regulatory Axis |
| title_full_unstemmed | An Analysis of AMPK and Ferroptosis in Cancer: A Potential Regulatory Axis |
| title_short | An Analysis of AMPK and Ferroptosis in Cancer: A Potential Regulatory Axis |
| title_sort | analysis of ampk and ferroptosis in cancer a potential regulatory axis |
| topic | ampk ferroptosis cancer energy metabolism iron homeostasis |
| url | https://www.imrpress.com/journal/FBL/30/7/10.31083/FBL36618 |
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