Human Gene Set: WACKER_HYPOXIA_TARGETS_OF_VHL


Standard name WACKER_HYPOXIA_TARGETS_OF_VHL
Systematic name M2371
Brief description Genes down-regulated by VHL [GeneID=7428] and re-expressed under hypoxia conditions in renal carcinoma cells.
Full description or abstract The von Hippel-Lindau tumor suppressor gene (VHL) is mutated in clear cell renal cell carcinomas (RCC), leading to the activation of hypoxia-inducible factor (HIF)-mediated gene transcription. Several VHL/HIF targets, such as glycolysis, angiogenesis, cell growth, and chemotaxis of tumor cells, have been implicated in the transformed phenotype of RCC-regulating properties. Here, we show that VHL suppresses key features of cell transformation through downregulation of the HIF-dependent expression of activin B, a member of the transforming growth factor beta superfamily. Activin B expression is repressed by restoration of VHL in VHL-deficient RCC cells and upregulated by hypoxia. RCC tumor samples show increased expression of activin B compared to that in the normal kidney. VHL increases cell adhesion to the extracellular matrix, promotes cell flattening, and reduces invasiveness. These effects are completely phenocopied by RNA interference-mediated knockdown of activin B and reverted by treatment with recombinant activin B. Finally, knockdown of activin B reduces tumor growth of RCC cells in nude mice. Our data indicate that activin B is a key mediator of VHL/HIF-induced transformation in RCC.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 19158274   Authors: Wacker I,Sachs M,Knaup K,Wiesener M,Weiske J,Huber O,Akçetin Z,Behrens J
Exact source Table 1S
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Organism Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
Source platform HUMAN_GENE_SYMBOL
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Version history 3.1: First introduced

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