STANDARD_NAME	WACKER_HYPOXIA_TARGETS_OF_VHL
SYSTEMATIC_NAME	M2371
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WACKER_HYPOXIA_TARGETS_OF_VHL
NAMESPACE	HUMAN_GENE_SYMBOL
DESCRIPTION_BRIEF	Genes down-regulated by VHL [GeneID=7428] and re-expressed under hypoxia conditions in renal carcinoma cells.
DESCRIPTION_FULL	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.
PMID	19158274
GEOID	
AUTHORS	Wacker I,Sachs M,Knaup K,Wiesener M,Weiske J,Huber O,Akçetin Z,Behrens J
CONTRIBUTOR	Arthur Liberzon
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 1S
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	ADM,CA9,CCND1,CP,ENO2,HK2,IGFBP3,INHBB,P4HA1,PDK1,PFKP,TGFA,VEGF
GENE_SYMBOLS	ADM,CA9,CCND1,CP,ENO2,HK2,IGFBP3,INHBB,P4HA1,PDK1,PFKP,TGFA,VEGFA
FOUNDER_NAMES