Table 3.

CSC phenotypes that depend on OXPHOS to maintain cancer stemness and abnormally increased metabolites or metabolic pathway products as markers of CSC stemness promotion.

CSC phenotype	Abnormally increased metabolic intermediates as markers of CSC stemness promotion	Impacts of OXPHOS on CSC stemness	Impacts of OXPHOS on the quiescence/proliferation states of CSCs	Reference
Glioma	ATP	Inhibition of glycolysis has minimal effects on energy production in GSCs and progenitor cells. Compared with differentiated cells, GSCs show a higher mitochondrial reserve capacity	GSCs show less glycolytic and rely mainly on OXPHOS than proliferating cells	[93]
Glioblastoma	Unknown	Depletion of IMP2 in gliomasphere, which can depress the oxygen consumption rate and both complex I and complex IV activity, causes impaired clonogenicity in vitro and tumourigenicity in vivo	Inhibition of OXPHOS but not of glycolysis abolishes clonogenicity in slowly-proliferating primary glioblastoma sphere (gliomaspheres), an established in vitro model for CSC	[94]
Lung cancer	Mitochondrial deoxynucleotide triphosphate	The mitochondrial deoxyguanosine kinase is required for the biogenesis of respiratory complex I and mitochondrial OXPHOS, which in turn regulates CSC self-renewal through AMPK-YAP1 signaling	Genetic targeting of DGUOK using doxycycline-inducible CRISPR/Cas9 is able to inhibit OXPHOS activity and lung CSC proliferation	[95]
Pancreatic cancer	Unknown	The MYC/PGC-1a ratio determines the metabolic phenotype of CSCs	Inhibition of mitochondrial complex I exerted by metformin-induced apoptosis preferentially in CSC-enriched cultures while provoking its quiescence	[96]