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The Keystone Symposium on Metabolism and Cancer Progression, organized by Drs Eileen White, Chi van Dang and Craig Thompson, brought together approximately 600 scientists to discuss the connections between metabolism and tumorigenesis. The origins of this field date back 80 years, when Warburg first observed robust glycolysis in experimental tumors, and recent interest has been spurred on by discoveries that metabolism is controlled by oncogenes, and that specific metabolic alterations can prime cells for transformation or promote tumor growth. These advancements seem to validate Warburg's prediction that understanding metabolism will produce strategies to improve the diagnosis and treatment of cancer. This short article outlines some of the major themes that pervaded the meeting.
Interactions between metabolism & cell death
The conference was combined with a sister symposium on Cell Death Pathways, underscoring the growing integration between metabolic flux and cell fate. In one of the keynote lectures, Joan Brugge from Harvard (MA, USA) outlined the metabolic parameters that allow tumor cells to escape anoikis [1]. Karen Vousden of the Beatson Institute (Glasgow, UK) described how p53, a classical regulator of cell death and senescence, coordinates a metabolic response to genotoxic stress to prevent oxidative damage [2]. A number of other investigators discussed metabolic roles of the lysosomal degradative pathway autophagy in cancer cell survival and chemotherapy. Noboru Mizushima of the Tokyo Medical and Dental University (Tokyo, Japan) found that mosaic deletion of ATG5 , which encodes a protein involved in autophagosome formation, caused a highly penetrant phenotype of tumorigenesis in mice, but the tumors were restricted to the liver and were generally benign. Dr Mizushima contrasted this finding with the more widespread tumor formation observed in mice heterozygous for deletion of beclin-1 , another autophagy gene [3]. Eileen White from Rutgers University (NJ, USA) presented data regarding the complicated interplay between oncogene activation and the induction of autophagy, and how this might be exploited in cancer therapy. For example, suppressing the expression of Atg5 or Atg7 reduced the growth of xenografts derived from cells expressing the oncoprotein H-Ras V12. Finally, Reuben Shaw from The Salk Institute (CA, USA) provided compelling evidence for a novel mechanism linking metabolic stress with autophagy. The serine/threonine kinase Ulk1, a mammalian homolog of the yeast autophagy regulator Atg1, is...