15 Reprogramming energy metabolism in cancer Flashcards
What is the Warburg effect?
described increased lactate production by cells under aerobic conditions
How does the Warburg effect occur?
oncogene /TSG induced changes in proliferatice drive
Name 4 mediators of the Warburg effect
PTEN
TP53
c-Myc
K-Ras
What is PTEN?
TSG
What does loss of PTEN activity do?
AKT is activated
What does AKT do?
promotes proliferation, cell migration, and survival
increases glucose uptake via GLUT-4
increases glycolysis
How does p53 increase glycolysis?
hexokinase and PGM activation
How does p53 control oxidative phospharylation?
SCO2 -> funcitonal COX
Do p53 defficient or XS tissues exhibit the Warburg effect?
defficient
What happens if TP53 is mutated instead of knocked out?
retention of its ability to upregulate enzymes involved in…
detox oxidative stress
DNA/RNA synthesis
Oxidative ATP generation
Increased glucose consumption
What does c-Myc do?
Myc,MAX is bound to E box with TFI, both regulating genes in…
Lipogenesis
RNA, protein synthesis
Glucose and glutamine metabolism
Why is c-Myc amplification so good at driving proliferation?
Glutaminolysis offers a source of material where lots of AAs and FAs can be produced
supports entire width of metabolism
What does K-Ras do?
induces tumour cells to increase uptake of external protein
Which Warburg mediators are involved in pancreatic cancer?
K-Ras
TP53
Which 2 complexes in the electron transport chain are important in cancer?
succinate dehydrogenase mutations
fumarte hydratase mutations
