TABLE 2.

Regulation of metabolic genes in failing cardiomyocytes and cancer cells.

Gene	Failing cardiomyocyte	Cancer cell
Akt	• Akt is upregulated in the heart due to pressure-overload (Wende et al., 2015) • Repression of FAO (Wende et al., 2015)	• Akt pathway activation is leading to cell growth (Sancho et al., 2015) • Akt enhances glucose supply via GLUT-1 and HK1 upregulation (Barthel et al., 1999; Majewski et al., 2004)
PGC-1α	• Downregulation in heart failure (Arany et al., 2006) • Inhibition deteriorates heart function during pressure-overload (Arany et al., 2006)	• Upregulation in breast cancer increases glutamine flux and glycolysis rates (McGuirk et al., 2013) • PGC-1α positively regulates cellular respiration in the mitochondrium (Wu et al., 1999)
OGT/OGA (O-GlcNAc)	• Increased O-GlcNAc is protective in the diabetic heart (Marsh et al., 2011; Kronlage et al., 2019) • Inhibition of O-GlcNAc protects from pressure-overload (Umapathi et al., 2021)	• Decreased O-GlcNAc induces apoptosis and reduces growth of breast cancer and pancreatic tumors (Caldwell et al., 2010; Ma et al., 2013; Ferrer et al., 2014)
PFK	• Inhibition deteriorates heart function during pressure-overload (Wang et al., 2013)	• Upregulation in cancer and maintenance of a high glycolytic flux, e.g., in leukemia cells (Chesney et al., 1999)

FAO, Fatty acid oxidation; GLUT-1, Glucose transporter 1; HK, Hexokinase; PFK, Phosphofructokinase; PGC-1α, Peroxisome proliferator-activated receptor-gamma coactivator; Akt, Protein kinase B; O-GlcNAc, O-Linked N-Acetylglucosamine; OGT, Protein O-GlcNAc Transferase; OGA, protein O-GlcNAcase; TopoIIβ, Topoisomerase IIβ; VEGF, Vascular endothelial growth factor.