Clear cell renal cell carcinoma pathways (WP4018)
Homo sapiens
Inactivation of VHL due to mutation or DNA methylation is an early event in ccRCC that leads to accumulation of the transcription factor HIF-α, which dimerizes with HIF-β and translocates to the nucleus. The resulting HIF-α–HIF-β-induced up-regulation of downstream genes promotes cell proliferation, glucose uptake, glycolysis, and angiogenesis. Mutations in chromatin remodelers and histone modifiers including PBRM1, SETD2, BAP1 and KDM5C lead to global abnormal gene expression patterns, and deficiency in DNA repair, which contributes to genomic instability. Activation of PI3K–mTOR signaling promotes cell proliferation and tumor aggression, and increases translation of HIF-α, leading to enhanced HIF-α-mediated gene expression. The proposed development pattern of ccRCC is based on tumor evolution analyses and current understanding of genomic variation. Description adapted from "Precision medicine from the renal cancer genome", Riazalhosseini and Lathrop. Additional sources of information: mTORC1 complex is based on [https://en.wikipedia.org/wiki/Mechanistic_target_of_rapamycin#mTORC1 Wikipedia]. PDGFB and TGFB as targets of HIF1A based on [http://www.genome.jp/kegg-bin/show_pathway?hsa05211 KEGG]. Phosphorylation sites were added based on information from PhosphoSitePlus (R), www.phosphosite.org.
Authors
Alex Pico , Kristina Hanspers , Egon Willighagen , and Eric WeitzActivity
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Organisms
Homo sapiensCommunities
CPTAC Diseases Renal Genomics PathwaysAnnotations
Cell Type Ontology
kidney cell kidney proximal convoluted tubule epithelial cellDisease Ontology
clear cell renal cell carcinomaPathway Ontology
signaling pathwayReferences
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