A proliferative cell needs to control their needs in DNA and RNA. It has emerged recently that many of the genetic factors commonly altered in cancer cells target metabolic genes and especially nucleotide synthesis. An altered metabolism allows cancer cells to sustain their proliferative needs. However, understanding a cancer cell drive the nucleotide synthesis remains to be explored. We propose to elucidate by which molecular mechanisms cancer cells drive and sense nucleotide synthesis to promote cell proliferation. We will measure metabolite concentrations and metabolic fluxes in tumorigenic versus non-malignant cells in vitro, to systematically identify metabolic states that are sufficient to drive an oncogenic transformation. Subsequently, we will map them in vivo onto metabolic states quantified in a diet and carcinogen induced mouse model, with the final goal to unravel the causal link between the increased cancer risk and the metabolic syndrome. Elucidating this metabolic interface will provide a mechanistic understanding of tumor initiating events in patients suffering from the metabolic syndrome and ultimately lead to new therapeutic strategies to prevent increased tumor events in such patients.
|Effective start/end date||7/11/17 → 12/31/19|
- National Cancer Institute (5R00CA194192-05)
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