Fig. 5.

An overview of the metabolic features unique to ccRCC in the landscape of cancer metabolic regulation. The figure shows reporter pathways (represented by edges; refer to Fig. 2) and metabolites (represented by nodes; refer to SI Appendix, Fig. S16) transcriptionally regulated only in ccRCC vs. matched tumor-adjacent normal tissue; and subnetworks (represented by rectangles) that feature lack of gene redundancy only in ccRCC metabolic network (refer to Fig. 4A). The mechanisms that contribute to this metabolic phenotype are summarized. First, loss of VHL represses expression of metabolic genes in alanine, aspartate, glutamate, and branched-chain amino acids metabolism. Second, potential activation of STAT1 up-regulates redundant genes in nucleotide biosynthesis and inositol metabolism. Third, loss of heterozygosity in metabolic genes adjacent to VHL affects several pathways previously identified as down-regulated or deficient only in ccRCC (represented by double bar).