Metabolic Regulation in Cancer Stem Cells
Summary
Cancer stem cells (CSCs) represent a distinct subpopulation within tumours, endowed with self-renewal capacity, tumour initiation potential and pronounced resistance to conventional therapies. Central to their biology is the reprogramming of metabolic pathways, enabling CSCs to adapt to fluctuating nutrient and oxygen availability. Unlike bulk tumour cells that often rely predominantly on glycolysis, CSCs can flexibly engage oxidative phosphorylation (OXPHOS) or fatty acid oxidation (FAO), and exploit lipid storage and mobilisation according to microenvironmental signals. This metabolic plasticity not only fulfils bioenergetic and biosynthetic demands but also influences redox balance and epigenetic regulation, reinforcing stemness programmes. Key regulatory nodes—such as transcription factors, nutrient-sensing kinases and ion transporters—coordinate shifts between glycolysis, the tricarboxylic acid (TCA) cycle and lipid pathways. By targeting these vulnerabilities, recent studies have demonstrated that inhibition of specific metabolic enzymes or restoration of mitochondrial function can sensitize CSCs to chemotherapy, impede metastatic dissemination and prevent tumour relapse. Such insights underscore the global significance of metabolic regulation as both a fundamental feature of CSC biology and a promising avenue for novel therapeutic strategies.
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Metabolic Regulation in Cancer Stem Cells publication trend
The graph below shows the total number of articles in metabolic regulation in cancer stem cells across all publications each year (not limited to Nature Index journals).
Technical terms
Cancer Stem Cells (CSCs): A subset of tumour cells with the capacity for self-renewal, differentiation and sustained tumour propagation.
Glycolysis: A cytosolic pathway that converts glucose into pyruvate, producing ATP and metabolic intermediates.
Oxidative Phosphorylation (OXPHOS): A mitochondrial mechanism by which electrons flow through the respiratory chain to drive ATP synthesis.
Fatty Acid Oxidation (FAO): The mitochondrial β-oxidation of fatty acids, yielding acetyl-CoA for the TCA cycle and reducing equivalents.
Lipid Droplets: Intracellular organelles storing neutral lipids, serving as energy reserves and signalling hubs.
Tricarboxylic Acid (TCA) Cycle: A series of mitochondrial enzymatic reactions that oxidise acetyl-CoA to generate NADH and FADH₂ for OXPHOS.
Zinc Transporter: A membrane protein mediating zinc influx, whose modulation can influence mitochondrial enzyme activity.
References
- Loss of OVOL2 in Triple‐Negative Breast Cancer Promotes Fatty Acid Oxidation Fueling Stemness Characteristics. Advanced Science (2024).
- Glycerol‐3‐phosphate acyltransferase 3‐mediated lipid droplets accumulation confers chemoresistance of colorectal cancer. MedComm (2024).
- Estrogen-related receptor alpha (ERRα) controls the stemness and cellular energetics of prostate cancer cells via its direct regulation of citrate metabolism and zinc transportation. Cell Death & Disease (2025).
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