cancer metabolism Flashcards
what is quiescence?
state where the cell is not dividing
what is the definition of the Warburg Effect?
a shift in metabolism observed in most cancer cells, where energy is preferentially obtained by glycolysis and lactate fermentation, even in the presence of oxygen, instead of oxidative phosphorylation
what are the main metabolic features of cancer cells?
- energy is preferentially obtained through glycolysis
- pathway is activated independently of oxygen presence
- oxidative phosphorylation is reduced
- fatty acid oxidation is reduced
- biosynthesis is increased
what are the advantages of the Warburg effect?
- increased biosynthesis of molecules for cell division
- anti apoptotic effects - reduction in ROS due to decreased OXPHOS
- production of metabolites that participate in signalling
what are the advantages of the Warburg effect on the other hallmarks?
- reduced apoptosis
- increased growth/division
- increased angiogenesis
- increased invasion and metastasis
- reduced immune response
what are the possible causes of the Warburg Effect?
- anomalous mitochondria physiology
- direct consequences of higher division rates
- low oxygen in most tumour environments favour glycolysis
- deregulation of the expression of genes involved in metabolism
how might higher division rates underly the Warburg effect?
oncogenes like Akt or Myc reprogram metabolism to increase nutrient uptake, which increases glycolysis/lactate fermentation and biosynthesis
what constitutes hypoxia?
<10 mmHg [O2]
how do cancer cells respond to hypoxia?
- induction of angiogenesis to increase blood supply
- increase in glycolysis
these responses are mediated by up-regulation of HIF-1a
what is HIF-1a?
transcription factors activated when oxygen levels are too low
how does HIF-1a expression differ with oxygen concentration?
expression is exponentially increased with decreasing O2
How is HIF-1a inhibited?
prolyl hydroxylases hydroxylate HIF-1a, preventing formation of the HIF-1a heterodimer and induction of target genes. allowing binding of HIF-1a to pVHL
what is pVHL?
von hippel Lindau protein - targets hydroxylated HIF-1a for proteasomal degradation
