title: Autophagy, Warburg, and Warburg reverse effects in human cancer.
abstract: 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 frequently associated with a deviation of a set of energy generation mechanisms to a nonoxidative breakdown of glucose. This cellular phenomenon seems to rely on a respiratory impairment, linked to mitochondrial dysfunction. This mitochondrial dysfunction results in a switch to anaerobic glycolysis. It has been recently suggested that epithelial cancer cells may induce the Warburg effect in neighboring stromal fibroblasts in which autophagy was activated. These series of observations drove to the proposal of a putative reverse Warburg effect of pathophysiological relevance for, at least, some tumor phenotypes. In this review we introduce the autophagy process and its regulation and its selective pathways and role in cancer cell metabolism. We define and describe the Warburg effect and the newly suggested "reverse" hypothesis. We also discuss the potential value of modulating autophagy with several pharmacological agents able to modify the Warburg effect. The association of the Warburg effect in cancer and stromal cells to tumor-related autophagy may be of relevance for further development of experimental therapeutics as well as for cancer prevention.
authors.affiliation: Institute of Biochemistry and Molecular Medicine, National Council for Scientific and Technological Research, School of Pharmacy and Biochemistry, University of Buenos Aires, Junin 956 p5, 1113 Buenos Aires, Argentina ; Department of Pharmacology, CEMIC University Institute, 1113 Buenos Aires, Argentina.
authors.forename: Claudio D
authors.initials: CD
authors.lastname: Gonzalez
authors.affiliation: Institute of Biochemistry and Molecular Medicine, National Council for Scientific and Technological Research, School of Pharmacy and Biochemistry, University of Buenos Aires, Junin 956 p5, 1113 Buenos Aires, Argentina.
authors.forename: Silvia
authors.initials: S
authors.lastname: Alvarez
authors.affiliation: Institute of Biochemistry and Molecular Medicine, National Council for Scientific and Technological Research, School of Pharmacy and Biochemistry, University of Buenos Aires, Junin 956 p5, 1113 Buenos Aires, Argentina.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Ropolo
authors.affiliation: Department of Pharmacology, CEMIC University Institute, 1113 Buenos Aires, Argentina.
authors.forename: Carla
authors.initials: C
authors.lastname: Rosenzvit
authors.affiliation: Department of Pharmacology, CEMIC University Institute, 1113 Buenos Aires, Argentina.
authors.forename: Maria F Gonzalez
authors.initials: MF
authors.lastname: Bagnes
authors.affiliation: Institute of Biochemistry and Molecular Medicine, National Council for Scientific and Technological Research, School of Pharmacy and Biochemistry, University of Buenos Aires, Junin 956 p5, 1113 Buenos Aires, Argentina.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Vaccaro
mesh_terms: D001343:Autophagy; D006019:Glycolysis; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*