UC Berkeley

Cancer cells possess fundamentally altered metabolic pathways that provide a foundation to support tumorigenicity and malignancy. Our understanding of the biochemical underpinnings of cancer has benefited from the integrated utilization of large-scale profiling platforms (e.g., genomics, proteomics, and metabolomics), which, together, can provide a global assessment of how enzymes and their parent metabolic networks become altered in cancer to fuel tumor growth. In chapter one, we present several examples of how these integrated platforms have yielded fundamental insights into dysregulated metabolism in cancer. We will also discuss questions and challenges that must be addressed to more completely describe, and eventually control, the diverse metabolic pathways that support tumorigenesis.

In chapters two and three, using genomic and functional metabolomic platforms, we elucidate the role of two novel metabolomic pathways in promoting the aggressive features of cancer. In chapter two, we show that inositol phosphate recycling can fuel cancer aggressiveness by controlling both glycolytic and lipid metabolism. In chapter three, we use functional metabolomics to discover that the ether lipid generating enzyme, AGPS, is both necessary and sufficient to promote cancer malignancy by maintaining the balance between structural and signaling lipids in the cell. Taken together these studies not only highlight the application of genomics and functional metabolomics in uncovering novel metabolomic pathways that drive cancer malignancy, but they also pave the way for the development of novel metabolism-based chemotherapeutic strategies that may some day be used in the clinic to treat malignant human cancers.