Modulating autophagy and the ?reverse Warburg effect?

VACCARO, M. INÉS; GONZALEZ, CLAUDIO; ALVAREZ, SILVIA; ROPOLO, ALEJANDRO

Tumor Metabolome Targeting and Drug Development

Springer

Lugar: NY; Año: 2014; p. 131 - 156

Autophagy is a highly regulated cellular pathway for degrading long- [AQ1] 45 lived proteins and is the only known pathway for clearing cytoplasmic organelles.6 Autophagy is a major contributor to maintain cellular homeostasis and metabolism.7 The quality control of mitochondria is essential to maintain cell energy and this pro8cess appears to be achieved via autophagy.Warburg hypothesized that cancer growth9 is caused by the fact that tumor cells mainly generate energy by the non-oxidative10 breakdown of glucose. This cellular behavior relies on a respiratory impairment,11 characterized by a mitochondrial dysfunction, which results in a switch to glycoly12sis. Moreover, epithelial cancer cells may induce theWarburg effect in neighboring13 stromal fibroblasts in which autophagy was activated. Here, we introduce the au14tophagy process, its regulation, the selective pathways, and its role in cancer cell15 metabolism. We define the Warburg effect and the ?reverse? hypothesis and we16 discuss the potential value of modulating autophagy. The association of the War17burg effect in tumor and stromal cells to cancer-related autophagy is of significant18 relevance in experimental therapeutics