L12-Reprogramming energy metabolism in cancer Flashcards
What is the main route of energy generation for normal cells and for cancerous cells?
Normally cells will undergo oxidative phosphorylation whereas cancer cells switch to increased glycolysis. However it is not an on or off switch, just a shift between the two depending on available resources
Why do cancer cells require lots of energy?
For proliferation and to avoid apoptosis.
What is the walberg effect?
It describes an increased production of lactate under aerobic conditions. It cannot occur in hypoxia. e.g. this means more anaerobic respiration is happening but under aerobic conditions.
How does mutated Pten cause an increase in the walberg effect?
Pten normally limits conversion of PIP2 to PIP3 in the PI3K pathway. When it is mutated it does not limit this step and ends up with lots of PIP3 being produced which produces AKT and mTOR. AKT infuences glucose uptake of the cell for proliferation so unlimited activity of AKT causes massive glucose uptake. This massive increase in glucose causes more glycolysis and hence more lactate production.
How does lack of p53 cause an increase in the walberg effect?
P53 is a transcription factor that when mutated or absent will affect cell proliferation. p53 controls oxidative phosphorylation through SCO2 protein that is required for oxidative phosphorylation. With lack of p53 end up with less SCO2 and hence less oxidative phosphorylation. As the oxidative phosphorylation pathway cannot occur this results in increased glycolysis and the walberg effect.
How does c-myc upregulation increase the walberg effect?
It increases glutamine metabolism to increase protein production at ribosomes. This causes increased lactate and hence an increase in the walberg effect.
How can k-ras mutations lead to an increase in the walberg effect?
k-ras induces tumour cells to increase uptake of external proteins by pinocytosis. It also increases glycolysis through AKT activation which leads to increased walberg effect.
