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Tumor Metabolome Targeting and Drug Development pp 131–156Cite as

Modulating Autophagy and the “Reverse Warburg Effect”

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Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

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.

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Acknowledgments

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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Authors and Affiliations

  1. CONICET, Buenos Aires, Argentina

    Prof. Dr. Maria I. Vaccaro PhD, AGAF

  2. Institute for 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

    Prof. Dr. Maria I. Vaccaro PhD, AGAF, Claudio D. Gonzalez MD, Silvia Alvarez PhD & Alejandro Ropolo PhD

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  1. Prof. Dr. Maria I. Vaccaro PhD, AGAF
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  2. Claudio D. Gonzalez MD
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  3. Silvia Alvarez PhD
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  4. Alejandro Ropolo PhD
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Correspondence to Maria I. Vaccaro PhD, AGAF .

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  1. Vice President, Biology, Arrowhead Research Corporation, 465 Science Drive, 53711 Madison, USA

    Steven Kanner

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Vaccaro, M., Gonzalez, C., Alvarez, S., Ropolo, A. (2014). Modulating Autophagy and the “Reverse Warburg Effect”. In: Kanner, S. (eds) Tumor Metabolome Targeting and Drug Development. Cancer Drug Discovery and Development. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9545-1_6

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