Autophagy, Warburg, and Warburg reverse effects in human cancer

GONZÁLEZ, CLAUDIO; ALVAREZ, SILVIA; ROPOLO, ALEJANDRO; ROSENZVIT, CARLA; GONZALEZ BAGNES, MARÍA F.; VACCARO, M. INÉS

BioMed Research International

Hindawi Publishing Corporation

Lugar: New York; Año: 2014 vol. 2014 p. 1 - 10

2314-6133

Autophagy is a highly regulated-cell pathway for degrading long-lived proteins as well as for clearing cytoplasmic organelles.Autophagy is a key contributor to cellular homeostasis and metabolism. Warburg hypothesized that cancer growth is frequentlyassociated with a deviation of a set of energy generation mechanisms to a nonoxidative breakdown of glucose. This cellularphenomenon seems to rely on a respiratory impairment, linked to mitochondrial dysfunction. This mitochondrial dysfunctionresults in a switch to anaerobic glycolysis. It has been recently suggested that epithelial cancer cells may induce the Warburgeffect in neighboring stromal fibroblasts in which autophagy was activated.These series of observations drove to the proposal of aputative reverse Warburg effect of pathophysiological relevance for, at least, some tumor phenotypes. In this review we introducethe autophagy process and its regulation and its selective pathways and role in cancer cell metabolism.We define and describe theWarburg effect and the newly suggested ?reverse? hypothesis. We also discuss the potential value of modulating autophagy withseveral pharmacological agents able to modify the Warburg effect. The association of the Warburg effect in cancer and stromalcells to tumor-related autophagy may be of relevance for further development of experimental therapeutics as well as for cancerprevention.