Reactive oxygen species produced by altered tumor metabolism impacts cancer stem cell maintenance
Kaysaw Tuy1, Lucas Rickenbacker1, Anita B Hjelmeland1
1Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
Abstract:
Controlling reactive oxygen species (ROS) at sustainable levels can drive multiple facets of tumor biology, including within the cancer stem cell (CSC) population. Tight regulation of ROS is one key component in CSCs that drives disease recurrence, cell signaling, and therapeutic resistance. While ROS are well-appreciated to need oxygen and are a product of oxidative phosphorylation, there are also important roles for ROS under hypoxia. As hypoxia promotes and sustains major stemness pathways, further consideration of ROS impacts on CSCs in the tumor microenvironment is important. Furthermore, glycolytic shifts that occur in cancer and may be promoted by hypoxia are associated with multiple mechanisms to mitigate oxidative stress. This altered metabolism provides survival advantages that sustain malignant features, such as proliferation and self-renewal, while producing the necessary antioxidants that reduce damage from oxidative stress. Finally, disease recurrence is believed to be attributed to therapy resistant CSCs which can be quiescent and have changes in redox status. Effective DNA damage response pathways and/or a slow-cycling state can protect CSCs from the genomic catastrophe induced by irradiation and genotoxic agents. This review will explore the delicate, yet complex, relationship between ROS and its pleiotropic role in modulating the CSC.
Insights
Reactive oxygen species (ROS) play a critical role in cancer stem cell (CSC) survival, proliferation, and therapeutic resistance. Understanding ROS regulation under both normoxia and hypoxia is key to targeting CSCs and preventing disease recurrence.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Reactive oxygen species (ROS) are crucial regulators of tumor biology, impacting cancer stem cells (CSCs).
- ROS are involved in CSC signaling, disease recurrence, and therapeutic resistance.
- The role of ROS extends to hypoxic conditions, influencing stemness pathways.
Purpose of the Study:
- To explore the complex relationship between ROS and CSCs.
- To elucidate the pleiotropic roles of ROS in modulating CSCs within the tumor microenvironment.
- To highlight the significance of ROS in cancer recurrence and therapeutic resistance.
Main Methods:
- Literature review of existing research on ROS, hypoxia, and CSCs.
- Analysis of metabolic shifts and antioxidant mechanisms in cancer.
- Examination of CSC quiescence and redox status in relation to therapy resistance.
Main Results:
- ROS regulation is vital for CSCs, influencing proliferation, self-renewal, and survival.
- Hypoxia modulates ROS levels, impacting stemness pathways and CSC behavior.
- Altered cancer metabolism, including glycolytic shifts, aids CSC survival by mitigating oxidative stress.
- Therapy-resistant CSCs exhibit altered redox states and may be quiescent, contributing to disease recurrence.
Conclusions:
- ROS have a dual role in cancer, influencing CSCs under both normoxic and hypoxic conditions.
- Targeting ROS and associated metabolic pathways presents a potential strategy to overcome CSC-mediated therapeutic resistance and recurrence.
- Further research into the intricate ROS-CSC interplay is essential for developing effective cancer therapies.
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