Mitochondria and Metabolism in Cancer Stem Cells (CSCs)

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Stem Cells".

Deadline for manuscript submissions: 15 March 2025 | Viewed by 769

Special Issue Editors


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Guest Editor
Translational Medicine, School of Science, Engineering and the Environment (SEE), University of Salford, Greater Manchester, Salford M5 4WT, UK
Interests: cancer stem cells; cancer metabolism; tumour recurrence and metastasis; drug resistance; clinical trials
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Guest Editor
1. Department of Oncology, Georgetown University Medical Center, Washington, DC 20057, USA
2. Center for Translational Imaging, Georgetown University Medical Center, Washington, DC 20057, USA
3. Department of Radiology, Georgetown University Medical Center, Washington, DC 20057, USA
Interests: cancer biology; drug resistance; GI cancers; imaging sciences; magnetic resonance imaging (MRI); neurologic; brain; CNS cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue of Cells will focus on the basic science and translational aspects of cancer metabolism, with a particular emphasis on energy metabolism and metabolic re-programing in cancer cells. This broadly includes mitochondrial, glycolytic, and fatty acid metabolism, as well as other areas of metabolism. We are also interested in how driver mutations, gene expression, and epigenetic regulation influence metabolism in cancer cells. Metabolic re-programing is the process by which metabolic pathways are altered in the various phases of cancer development, including tumor initiation, progression, and metastasis. Metabolic re-programing occurs in tumor cells, dormant tumor cells (DTCs), cancer stem cells (CSCs), circulating tumor cells (CTCs), and tumor-initiating cells (TICs), as well as in cells that form part of the tumor microenvironment. Hence, metabolic reprograming is a key therapeutic target for the prevention of cancer development and the prevention of tumor recurrence and metastasis. Chemo-resistance and radio-resistance are thought to underlie treatment failure and poor clinical outcome in cancer patients. In this context, the metabolic mechanism(s) underpinning treatment failure have been attributed to metabolic flexibility. As a result of metabolic flexibility, cancer cells can change their preference for particular metabolic fuel sources, allowing them to survive and even thrive under harsh conditions.

This Special Issue provides an open access forum to compile a collection of original research and review articles on the role of metabolism and mitochondrial function in the cellular pathogenesis of cancer, drug resistance, and metastasis, with an emphasis on cancer stem cells and disease mechanisms.  We welcome submissions on a wide range of research topics, including the relationship between cancer stem cells and other metabolic processes, including oxidative stress and superoxide production, as well as the cell cycle, glycolysis, aging, and senescence.

Dr. Michael Lisanti
Dr. Christopher Albanese
Guest Editors

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Keywords

  • cancer stem cells
  • circulating tumor cells
  • drug resistance
  • metabolism
  • mitochondria
  • OXPHSOS
  • mitochondrial DNA (mtDNA)
  • glycolysis
  • cell cycle
  • DNA damage
  • other metabolic processes
  • oxidative stress
  • senescence
  • therapeutic approaches

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Published Papers (1 paper)

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Research

20 pages, 3497 KiB  
Article
ALDHHigh Breast Cancer Stem Cells Exhibit a Mesenchymal–Senescent Hybrid Phenotype, with Elevated Metabolic and Migratory Activities
by Luis Larrea Murillo, Conor J. Sugden, Bela Ozsvari, Zahra Moftakhar, Ghada S. Hassan, Federica Sotgia and Michael P. Lisanti
Cells 2024, 13(24), 2059; https://doi.org/10.3390/cells13242059 - 13 Dec 2024
Viewed by 451
Abstract
Cancer stem cells (CSCs) account for 0.01 to 2% of the total tumor mass; however, they play a key role in tumor progression, metastasis and resistance to current cancer therapies. The generation and maintenance of CSCs are usually linked to the epithelial–mesenchymal transition [...] Read more.
Cancer stem cells (CSCs) account for 0.01 to 2% of the total tumor mass; however, they play a key role in tumor progression, metastasis and resistance to current cancer therapies. The generation and maintenance of CSCs are usually linked to the epithelial–mesenchymal transition (EMT), a dynamic process involved in reprogramming cancer cells towards a more aggressive and motile phenotype with increased stemness potential. Cells that undergo an EMT process have shown to be more resistant to conventional chemo/radiotherapies. In this context, aldehyde dehydrogenase (ALDH) enzymes, known for their role in the cellular detoxification of aldehydes and enhancement of cell survival, are often upregulated in cancer cells, promoting their resistance to conventional cancer treatments. Indeed, high ALDH levels have become a hallmark biomarker of CSCs and are often used to isolate this sub-population from the more abundant cancer cell populations. Herein, we isolated human breast cancer epithelial cells with higher ALDH abundance (ALDHHigh) and compared them to those with low ALDH abundance (ALDHLow). ALDHHigh sub-populations exhibited more characteristic EMT biomarkers by adopting a more mesenchymal phenotype with increased stemness and enhanced migratory potential. Furthermore, ALDHHigh sub-populations displayed elevated senescent markers. Moreover, these cells also demonstrated higher levels of mitochondria DNA/mass, as well as greater mitochondrial and glycolytic metabolic function. Conversely, ALDHLow sub-populations showed a higher efficiency of mammosphere/colony formation and an increased proliferative capacity. Therefore, we demonstrated that these ALDH sub-populations have distinct characteristics, underscoring their role in EMT, the formation of tumors and the mechanisms of metastasis. Full article
(This article belongs to the Special Issue Mitochondria and Metabolism in Cancer Stem Cells (CSCs))
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