Grants and Contracts Details

Description

Our recently published study suggests a new role for DEK in cellular metabolism. In that study, performed in normal and transformed keratinocytes, Seahorse flux analyses demonstrate that DEK OE stimulates glycolysis and cellular potential for oxidative phosphorylation (oxphos) ¡V key biosynthetic and energy processes required to enable and sustain cancer cell growth. Further, NMR-based metabolomics studies detected small metabolites that participate in glycolysis and the TCA cycle that produce precursors for oxphos. Specifically, DEK OE caused a marked decrease in glucose and an increase in glycolytic end products (lactate, alanine and NAD+); in the transformed cells, it also stimulated accumulation of TCA cycle intermediates. Importantly, the metabolic changes in both normal and transformed cells occurred in the absence of proliferative gains. These novel flux and NMR data suggest that DEK drives metabolic reprogramming that enables, rather than follows, cellular proliferation. The major goals of this component of the proposal are to define the metabolic consequences of overexpression or knockdown of the oncogene DEK in head and neck squamous cell carcinomas. The DEK-dependent stimulation of glycolysis and additional reprogramming of metabolism can only be unequivocally defined by stable isotope resolved metabolomics (SIRM). We will track DEK dependent sources of carbon and nitrogen as a basis to identify key nodes that support proliferation in the normal and oncogenically challenged epidermis. Here we will apply the Stable Isotope Resolved Metabolomics (SIRM) approach coupled with NMR and high-resolution mass spectrometry to generate an atom-resolved metabolic map of DEK OE to define the relative contributions of Wnt/ƒÒ-catenin signaling to key metabolic nodes, and test the functional role of relevant metabolites and enzymes in DEK-stimulated epidermal proliferation and oncogenesis.
StatusActive
Effective start/end date12/1/1911/30/24

Funding

  • Cincinnati Childrens Hospital Medical Center: $165,175.00

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