Table 1.

Factors that promote or regulate the metabolic reprograming of CSCs or cancer cells with stemness features in breast tumors.

Factor/regulatory molecule(s)	Induced metabolic process(es)	Mechanism of action
AMPK	Glycolysis, oxidative phosphorylation	Master metabolic regulator sensor for adaptations relative to energy and stress levels (46, 49, 52).
EMT gene signature and genes (e.g., Snail, TWIST1, ZEB1, ZEB2)	Glycolysis	Associated with downregulation of oxidative phosphorylation (37–41).
FBP1	Oxidative phosphorylation	Glycolytic antagonist, negative regulator of HIF1α and PKM2 (53). Epigenetic silencing promotes glycolysis, and decreased oxygen consumption and ROS production (37).
FGF13-AS1	Oxidative phosphorylation	LncRNA, inhibits stemness and glycolysis by reducing the half-life of c-Myc transcript (pro-glycolytic and stemness transcription factor) (54).
H19	Glycolysis	In hypoxia, H19 sponges miRNA let-7 leading to upregulation of pro-glycolytic HIF-1α and PDK1 (55).
HIF-1α	Glycolysis, oxidative phosphorylation	Master metabolic regulator and transcription factor that upregulates glucose transporters and glycolytic enzymes, including PDK1 and PKM2 (37, 53, 55, 56). Also promoted the shift toward oxidative epithelial-like CSC state (46).
Hypoxia	Glycolysis, oxidative phosphorylation	Stressor, inducer of pro-glycolytic transcription factors and ncRNAs (37, 55–57). Also promoted the transition to an oxidative epithelial-like breast CSC state (46)
let-7	Oxidative phosphorylation	MiRNA that downregulates pro-glycolytic HIF-1α (55).
miR-21	Glycolysis	MiRNA that regulates both EMT and overexpression of HIF-1α (58).
PDK1	Glycolysis	Glycolytic enzyme, inhibits pyruvate to acetyl CoA conversion, leading to reduced oxidative phosphorylation (55).
PGC-1α	Oxidative phosphorylation	Co-transcriptional regulator that induces mitochondrial biogenesis by activating transcription factors (49–51, 59).
PKM2	Glycolysis	Glycolytic enzyme, production of glycolytic intermediates for biomass production (37, 52).
ROS	Oxidative phosphorylation	Stressor, promotes the transition from a glycolytic mesenchymal-like CSC state to an oxidative epithelial-like breast CSC state (46).
Snail-G9a-DNMT	Glycolysis	Chromatin modifying complex which mediates the repressive histone methylation/deacetylation and DNA methylation, of the FBP1 promoter, which silences the glycolytic antagonist (37).