Tumor metabolism

Dr. Bernhard Radlwimmer

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Our group has been using screening approaches applied to either primary gliomas (Toedt 2011; Barbus 2011) or glioma-derived stem-cell like cultures (Ernst 2009; Ernst 2010; Goidts 2012), to identify sets of genes with potential use as tumor markers or therapy targets.We also showed that the mutation status of the metabolic enzyme IDH1 is a strong classifier defining two major groups of adult glioma that differ in their tumor pathomechanisms and tumor metabolism (Toedt 2011). Recently, we found that the subset of glioblastomas carrying wild-type IDH have increased expression of branched-chain amino acid transaminase 1 (BCAT1), the enzyme that initiates the catabolism of branched-chain amino acids (BCAAs). The expression of this enzyme is necessary for tumor growth and disease progression (Tonjes 2013). This suggests that BCAT1 and the involved metabolic pathway may be a way to target glioblastoma in individuals lacking tumor mutations in IDH1 or IDH2.

Perturbances of BCAA metabolism have been linked to a number of diseases including insulin resistance and heart disease; however, little is known about the role of BCAA catabolism in cancer. To address this question, we are looking to trace BCAA fate in glioblastoma cells by nonradioactive isotope tracing analysis and analyze signaling interactions and metabolite exchange between tumor and stroma cells. Furthermore, we are characterizing the epigenetic regulation of metabolic networks and the role of the feedback loops provided by the regulation of chromatin modifying enzymes by certain metabolites.

© dkfz.de

Dr. Bernhard Radlwimmer
Deputy Head of Department
Team Leader
E-Mail: b.radlwimmer@dkfz.de
Tel.: +49-6221-42-4580
Publications

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