Table 2.

CSC phenotypes that depend on glycolysis to maintain cancer stemness and the abnormally increased metabolites or metabolic pathway products as markers of enhanced CSC stemness and chemotherapy resistance.

CSC phenotype	Abnormally increased metabolic intermediates as markers of enhanced CSC stemness and chemotherapy resistance	Impacts of glycolysis on CSC stemness or chemotherapy resistance	Impacts of glycolysis on the quiescence/proliferation states of CSCs	Reference
Hepatocellular carcinoma	Lactate and glycolytic ability	The HIF1α/USP22 positive feedback loop upon TP53 inactivation strongly correlates with the CSC subpopulation	The HIF1α/USP22 positive feedback loop in promoting glycolysis and stemness on TP53 inactivation, which is known to control the balance between quiescence and proliferation in CSCs	[49]
Nasopharyngeal carcinoma	ROS and mitochondrial membrane potential	Glycolysis can sustain self-renewal, deter differentiation and enhance the antioxidant system in CSCs	Ungiven	[9]
Breast cancer	ROS	Co-inhibition of glycolysis and thioredoxin and GSH pathways suppresses tumor growth, tumor-initiating potential.	Metabolic or oxidative stress generated by 2DG, H2O2, or hypoxia promotes the transition of quiescent(ROSlo) M-BCSCs to a proliferative (ROShi) E-state.	[76]
Glioblastoma multiforme	Lactate	GBM, particularly the stem cell subpopulation, is sensitive to glycolytic inhibition via lactate dehydrogenase-A inhibitors	Dichloroacetate (100 μM), a compound capable of inhibiting glycolysis metabolism, is capable of hindering CSC proliferation (cell cycle arrest in G2/M phase)	[86]
Glioblastoma	Serine/glycine	Serine/glycine, as intermediates of glycolysis, participates in and promotes the synthesis of purine and thymidine, which are both precursors of RNA and DNA and induce progression of cell division	Hypoxia affects cancer cells in multiple intertwined ways: including a metabolic adaptation with overexpression of all glycolytic pathway enzymes for pyruvate/lactate synthesis and cell growth arrest coexisting with EMT.	[87]
Pancreatic cancer	ROS	Inhibition of glycolysis using 2-DG significantly enhances the cytotoxicity of gemcitabine and inhibits CSC and EMT phenotypes both in vitro and in vivo	Inhibition of glycolysis forces CSCs into the proliferative state and improves chemoresistance against gemcitabine.	[88]
Breast and prostate tumors	Glutamine and glutamate	using secreted frizzled-related protein 4 to inhibit glycolysis is sufficient to inhibit CSC survival in vivo.	Inhibition of glycolysis via sFRP4 makes CSCs vulnerable under conditions of variable glucose content.	[89]
Hepatocellular carcinoma	Mannose 6-phosphate, myo-Inositol-3-phosphate, fructose 6-phosphate, and glucose 6-phosphate	Increased activation of the pentose phosphate pathway diverts glycolytic intermediates to provide precursors for nucleotide synthesis	Ungiven	[90]
Pancreatic cancer	Lactate	Hepatocyte growth factor/c-MET/YAP/HIF-1α signaling enhances the expression of hexokinase 2 (HK2) and promotes glycolytic metabolism	HGF/c-MET/YAP/HIF-1α signaling enhanced the expression of Hexokinase 2 (HK2) and promoted glycolytic metabolism, which may facilitate CSC relatively quiescent state.	[91]
Breast cancer	Unknown	2-DG significantly inhibits the migration and invasion of Hs578Ts(i) and significantly decreases their ability to resist anoikis	Hs578Ts(i)8 showed an increased glycolysis preference and had a significantly increased proportion of cells with relatively quiescent CSC.	[92]