Modulating Autophagy and the “Reverse Warburg Effect”

  • Maria I. Vaccaro
  • Claudio D. Gonzalez
  • Silvia Alvarez
  • Alejandro Ropolo
Part of the Cancer Drug Discovery and Development book series (CDD&D)


Autophagy is a highly regulated cellular pathway for degrading long-lived proteins and is the only known pathway for clearing cytoplasmic organelles. Autophagy is a major contributor to maintain cellular homeostasis and metabolism. The quality control of mitochondria is essential to maintain cell energy and this process appears to be achieved via autophagy. Warburg hypothesized that cancer growth is caused by the fact that tumor cells mainly generate energy by the non-oxidative breakdown of glucose. This cellular behavior relies on a respiratory impairment, characterized by a mitochondrial dysfunction, which results in a switch to glycolysis. Moreover, epithelial cancer cells may induce the Warburg effect in neighboring stromal fibroblasts in which autophagy was activated. Here, we introduce the autophagy process, its regulation, the selective pathways, and its role in cancer cell metabolism. We define the Warburg effect and the “reverse” hypothesis and we discuss the potential value of modulating autophagy. The association of the Warburg effect in tumor and stromal cells to cancer-related autophagy is of significant relevance in experimental therapeutics.


Autophagy Cancer Warburg effect Mitochondria Caveolin Mitophagy Cancer cell metabolism Metformin Rapamycin Chloroquine mTOR PI3K VMP1 BECN1 ROS RAGE 



Our work is supported by grants from the Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT), the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), and the University of Buenos Aires.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Maria I. Vaccaro
    • 1
    • 2
  • Claudio D. Gonzalez
    • 2
  • Silvia Alvarez
    • 2
  • Alejandro Ropolo
    • 2
  1. 1.CONICETBuenos AiresArgentina
  2. 2.Institute for Biochemistry and Molecular Medicine, National Council for Scientific and Technological Research, School of Pharmacy and BiochemistryUniversity of Buenos AiresBuenos AiresArgentina

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