Regulation of Cancer Cell Metabolism

It is becoming more clear that oncogenic signalling pathways adapt tumor cell metabolism in order to support their growth and survival.

Normal cells have three basic needs if they wish to divide: rapid ATP generation to maintain energy status; increased biosynthesis of macromolecules; and tightened maintenance of appropriate cellular redox status.

To meet these needs, cancer cells have aquired alterations to the metabolism of all four major classes of macromolecules.

The Warburg Effect
The observation that most cancer cells predominantly produce energy by a high rate of glycolysis followed by lactic acid fermentation in the cytosol, rather than using oxidative phosphorylation.

Malignant, rapidly growing tumor cells typically have glycolytic rates up to 200x higher than those in normal tissue.

The shift from producing ATP from glycolysis rather than through oxidative phosphorylation demands that tumor cells implement an abnormally high rate of glucose uptake to meet their increased needs.

The PI3K Pathway
AKT (aka PKB) stimulates glycolysis by increasing the expression and membrane translocation of glucose transporters and by phosphorylating key glycolytic enzymes such as hexokineases.

Glut4 Transporters
Glut4 is the insulin-regulated glucose transporter that allows for the transport of glucose into the cell. On the cell membrane there are usually large complexes of these receptors shuttling in glucose from the environment.

The Glut4 transporter, however, needs to be traffiked to the membrane. The key protein that allows for the shuttling of the Glut4 transporter is PKB.