Uncovering the role of signaling pathways in the regulation of cellular metabolism


The initial discovery that cancer cells exhibit atypical metabolic characteristics can be traced to the pioneering work of Otto Warburg, over the first half of the twentieth century. Using isotopic tracing experiments, proteomics and genetic approaches, my lab investigates whether oncogenic signaling pathways could regulate metabolic pathways that supply small metabolites to sustain anabolic metabolism. In addition to nucleotide metabolism, we also study molecular connections between signaling pathways and global cancer cell metabolism. Molecular points of regulations of metabolic pathways mediated by oncogenic signals could give selective advantages to cancer cells to grow and proliferate.

Deciphering the interplay between oncogenic processes and metabolic pathways that contribute to metabolic reprogramming in a given setting may serve as a critical factor in determining therapeutic targets that yield greatest drug efficacy with marginal harmful effect on normal cells. Our research will enable further progress in the exploitation of unusual metabolic features in cancer as a means of therapeutic intervention.

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On the cover: Control of SAM abundance and RNA methylation by mTORC1 signaling. In this issue of Molecular Cell, Villa et al. report that mTORC1 promotes S-adenosylmethionine (SAM) synthesis and m6A RNA methylation to support protein synthesis and cell growth. The linear strand depicts the messenger RNA that requires SAM to be methylated to mediate its function. The woman operating the RNA machinery represents mTORC1, ensuring that RNA molecules are properly methylated to support biosynthesis. Image source: Emma Vidal (https://www.drawimpacts.com/).