Redox regulation of cancer stem cells: Biology and therapeutic implications

Abstract Cancer stem cells (CSCs) are a small group of tumor cells with the capacity to undergo self‐renewal and differentiation. These cells not only initiate and maintain tumor growth, but also confer resistance to current cancer therapies. CSCs display a high degree of plasticity and can be gener...

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Main Authors: Min Du, Jian Zhang, Max S. Wicha, Ming Luo
Format: Article
Language:English
Published: Wiley 2024-12-01
Series:MedComm – Oncology
Subjects:
Online Access:https://doi.org/10.1002/mog2.70005
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author Min Du
Jian Zhang
Max S. Wicha
Ming Luo
author_facet Min Du
Jian Zhang
Max S. Wicha
Ming Luo
author_sort Min Du
collection DOAJ
description Abstract Cancer stem cells (CSCs) are a small group of tumor cells with the capacity to undergo self‐renewal and differentiation. These cells not only initiate and maintain tumor growth, but also confer resistance to current cancer therapies. CSCs display a high degree of plasticity and can be generated under therapeutic stress via dedifferentiation from non‐stem‐like tumor cells, suggesting the necessity simultaneously targeting CSCs and bulk tumor cells to achieve the best therapeutic effect. Despite the findings that therapeutic stress induces CSC plasticity, the mechanisms underpinning CSC formation and therapeutic resistance are not fully defined. Tumor cells display elevated levels of reactive oxygen species (ROS), contributed by rapid proliferation, enhanced metabolic demands and oncogenic signaling. CSCs achieve redox homeostasis partly by regulating redox‐sensitive transcription factors (TFs), including NRF2, HIF‐1α, BACH1, NF‐kB, FOXOs, AP‐1, and others. This review aims to summarize the roles and underlying mechanisms of these TFs in regulation of CSCs and tumor progression from the perspectives of stem cell maintenance, metabolic reprogramming, epithelial–mesenchymal transition (EMT) and angiogenesis. We also discuss the potentials of utilizing specific inhibitors for these TFs in suppressing drug resistance and metastasis by repressing CSC activity, an approach that may provide new targeted therapies for advanced cancer and improve patient outcome.
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spelling doaj-art-967cca8e600a452aa7ef4a9013cbf3e62025-08-20T02:57:29ZengWileyMedComm – Oncology2769-64482024-12-0134n/an/a10.1002/mog2.70005Redox regulation of cancer stem cells: Biology and therapeutic implicationsMin Du0Jian Zhang1Max S. Wicha2Ming Luo3School of Medicine Southern University of Science and Technology Shenzhen ChinaSchool of Medicine Southern University of Science and Technology Shenzhen ChinaDivision of Hematology & Oncology, Department of Internal Medicine University of Michigan Ann Arbor Michigon USADepartment of Breast and Thyroid Surgery Peking University Shenzhen Hospital Shenzhen ChinaAbstract Cancer stem cells (CSCs) are a small group of tumor cells with the capacity to undergo self‐renewal and differentiation. These cells not only initiate and maintain tumor growth, but also confer resistance to current cancer therapies. CSCs display a high degree of plasticity and can be generated under therapeutic stress via dedifferentiation from non‐stem‐like tumor cells, suggesting the necessity simultaneously targeting CSCs and bulk tumor cells to achieve the best therapeutic effect. Despite the findings that therapeutic stress induces CSC plasticity, the mechanisms underpinning CSC formation and therapeutic resistance are not fully defined. Tumor cells display elevated levels of reactive oxygen species (ROS), contributed by rapid proliferation, enhanced metabolic demands and oncogenic signaling. CSCs achieve redox homeostasis partly by regulating redox‐sensitive transcription factors (TFs), including NRF2, HIF‐1α, BACH1, NF‐kB, FOXOs, AP‐1, and others. This review aims to summarize the roles and underlying mechanisms of these TFs in regulation of CSCs and tumor progression from the perspectives of stem cell maintenance, metabolic reprogramming, epithelial–mesenchymal transition (EMT) and angiogenesis. We also discuss the potentials of utilizing specific inhibitors for these TFs in suppressing drug resistance and metastasis by repressing CSC activity, an approach that may provide new targeted therapies for advanced cancer and improve patient outcome.https://doi.org/10.1002/mog2.70005cancer stem cells (CSCs)epithelial–mesenchymal plasticityreactive oxygen species (ROS)redox‐sensitive transcription factorstherapeutic resistance
spellingShingle Min Du
Jian Zhang
Max S. Wicha
Ming Luo
Redox regulation of cancer stem cells: Biology and therapeutic implications
MedComm – Oncology
cancer stem cells (CSCs)
epithelial–mesenchymal plasticity
reactive oxygen species (ROS)
redox‐sensitive transcription factors
therapeutic resistance
title Redox regulation of cancer stem cells: Biology and therapeutic implications
title_full Redox regulation of cancer stem cells: Biology and therapeutic implications
title_fullStr Redox regulation of cancer stem cells: Biology and therapeutic implications
title_full_unstemmed Redox regulation of cancer stem cells: Biology and therapeutic implications
title_short Redox regulation of cancer stem cells: Biology and therapeutic implications
title_sort redox regulation of cancer stem cells biology and therapeutic implications
topic cancer stem cells (CSCs)
epithelial–mesenchymal plasticity
reactive oxygen species (ROS)
redox‐sensitive transcription factors
therapeutic resistance
url https://doi.org/10.1002/mog2.70005
work_keys_str_mv AT mindu redoxregulationofcancerstemcellsbiologyandtherapeuticimplications
AT jianzhang redoxregulationofcancerstemcellsbiologyandtherapeuticimplications
AT maxswicha redoxregulationofcancerstemcellsbiologyandtherapeuticimplications
AT mingluo redoxregulationofcancerstemcellsbiologyandtherapeuticimplications