NIH Research Festival
Birt-Hogg-Dube syndrome (BHD) is caused by germline mutations in the FLCN gene, and patients are at risk of developing bilateral, multifocal renal tumors. Loss of heterozygosity of the FLCN locus and somatic “second hit” mutations are found in 17% and 53% of the renal tumors from patients with BHD syndrome, respectively . While multiple potential roles of FLCN have been uncovered in diverse pathways, such as AKT-mTOR pathway signaling, AMPK activation regulation, TFE3/TFEB transcriptional activation, etc. , there are few studies that have directly investigated the activity of central metabolic pathways such as glycolysis and the Krebs cycle in FLCN-deficient tumors and cells. In this study we utilized Stable Isotope Resolved Metabolomics (SIRM) to investigate and characterize the altered metabolic pathways in patient derived FLCN deficient cell lines. NMR as well as ultra-high-resolution mass spectrometry were used to analyze the polar/non-polar metabolites extracted from BHD renal tumor cells. Our preliminary data reveal that metabolic pathways including glycolysis, the Krebs cycle, pentose phosphate pathway, nucleotide synthesis and amino acid metabolism are altered in the FLCN deficient renal cancer cell lines compared with non-transformed human primary renal epithelial cells. These findings provide a novel perspective for selection of therapeutic agents for treatment and/or prevention of FLCN deficient renal cancer.
Scientific Focus Area: Molecular Biology and Biochemistry
This page was last updated on Friday, March 26, 2021