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|Title:||Understanding the Contribution of the Non-oxidative Pentose Phosphate Pathway to Cancer Cell Metabolism|
|Abstract:||Upregulation of the pentose phosphate pathway is heavily implicated in cancer cell growth and survival due to its involvement in the generation of NADPH for oxidative stress management and ribose-5-phosphate for nucleotide production. In this thesis, I use knockouts of the enzymes of the non-oxidative pentose phosphate pathway in order to investigate perturbations in the metabolisms of cancer cells. I found that ΔRPE, ΔTKT, and ΔPGD knockouts grow significantly slower than wildtype HCT-116 cancer cells, both in vitro and in vivo. I also discovered that enzymes of the non-oxidative pentose phosphate pathway control flux through the oxidative pentose phosphate pathway, and that the oxidative pentose phosphate pathway already overwhelms cellular requirements for ribose-5-phosphate. Rather than net producing ribose-5-phosphate from glycolytic intermediates by running the non-oxidative pentose phosphate pathway backwards, cancer cells utilize the non-oxidative pentose phosphate to shunt accumulating pentose-related metabolites into glycolysis. These results have important implications for future metabolism-based cancer therapies. Simultaneously targeting specific enzymes of the pentose phosphate pathway in tumors may increase the efficacy of traditional pharmaceutical interventions.|
|Type of Material:||Princeton University Senior Theses|
|Appears in Collections:||Chemistry, 1926-2019|
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