Sweetening of glutamine metabolism in cancer cells by Rho GTPases through convergence of multiple oncogenic signaling pathways

More than 60 years ago, Otto Warburg showed that cancer cells exhibit enhanced glycolysis accompanied by greatly elevated levels of lactate secretion, even in the presence of normal levels of oxygen (1). Warburg suggested that cancer cells arise from normal cells in a two-phase process: phase 1 is “injury” to the respiratory machinery (i.e., mitochondria), followed in phase 2 by enhanced “fermentation” (i.e., production of lactate from glucose) in the protoplasm (i.e., cytosol) (1).