Table 1.

Selected oncogenes and tumour suppressor genes that regulate metabolism⁴ (with permission)

Gene	Metabolic pathway	Relevance to RCC	Refs
PTEN	Inhibition of glycolysis through inactivation of Akt	2.6% of patients have biallelic loss and 16.6% of patients have monoallelic loss of PTEN Loss of PTEN is associated with high stage and grade of RCC	49,50
TSC1/2	Deficiency leads to the Warburg effect and glutamine addiction through activation of mTOR	Mutation is a risk factor for RCC	51,52
AKT	Upregulation of glycolysis through activation of enzymes including HK	Akt mutation is rare in RCC; activation is through PTEN loss. Akt inhibitors are being tested in clinical trials for RCC	53,54,55,56
VHL	Inhibition of the Warburg effect through deactivation of HIF	Loss-of-function mutation found in >90% of patients	57,58
p53	Downregulation of glycolysis by deactivation of GLUT1/4 and upregulation of TIGAR Upregulation of glutamine metabolism via increased transcription of GLS2	Mutation is rare in RCC	59,60,61,62
LKB1	Upregulation of glycolysis and β-oxidation and downregulation of lipid synthesis through activation of AMPK	Activity compromised in vitro, in vivo, and in patients	63,64,65
Myc	Upregulation of the Warburg effect through activation of HK, LDHA, and PDK1 Upregulation of glutamine metabolism through GLS1 activation Upregulation of lipid synthesis through activation of FAS and SCD1	Often mutated and overexpressed in RCC Activated by HIF-2α Overexpression induces RCC in mice	66,67,68,69 70

mTOR, mammalian target of rapamycin; HK, hexokinase; RCC, renal cell carcinoma; HIF, hypoxia-inducible factor; GLUT, glucose transporter; TIGAR, p53-inducible glycolysis and apoptosis regulator; GLS, glutaminase; APMK, AMP-activated protein kinase; LDHA, lactate dehydrogenase A; PDK1, pyruvate dehydrogenase kinase 1; FAS, fatty acid synthase; SCD1, Stearoyl-CoA desaturase 1.