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<MSIGDB BUILD_DATE="Jan 29, 2026" VERSION="2026.1.Hs" NAME="export">
    <GENESET STANDARD_NAME="WACKER_HYPOXIA_TARGETS_OF_VHL" SYSTEMATIC_NAME="M2371" HISTORICAL_NAMES="" PMID="19158274" AUTHORS="Wacker I,Sachs M,Knaup K,Wiesener M,Weiske J,Huber O,Akçetin Z,Behrens J" GEOID="" EXACT_SOURCE="Table 1S" GENESET_LISTING_URL="" EXTERNAL_DETAILS_URL="" CHIP="HUMAN_GENE_SYMBOL" CONTRIBUTOR="Arthur Liberzon" CONTRIBUTOR_ORG="MSigDB Team" 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." TAGS="" MEMBERS="ADM,CA9,CCND1,CP,ENO2,HK2,IGFBP3,INHBB,P4HA1,PDK1,PFKP,TGFA,VEGF" MEMBERS_SYMBOLIZED="ADM,CA9,CCND1,CP,ENO2,HK2,IGFBP3,INHBB,P4HA1,PDK1,PFKP,TGFA,VEGFA" MEMBERS_EZID="133,1356,2026,3099,3486,3625,5033,5163,5214,595,7039,7422,768" MEMBERS_MAPPING="ADM,ADM,133|CA9,CA9,768|CCND1,CCND1,595|CP,CP,1356|ENO2,ENO2,2026|HK2,HK2,3099|IGFBP3,IGFBP3,3486|INHBB,INHBB,3625|P4HA1,P4HA1,5033|PDK1,PDK1,5163|PFKP,PFKP,5214|TGFA,TGFA,7039|VEGF,VEGFA,7422" FILTERED_BY_SIMILARITY="" FOUNDER_NAMES="" REFINEMENT_DATASETS="" VALIDATION_DATASETS="" CATEGORY_CODE="C2" ORGANISM="Homo sapiens" SUB_CATEGORY_CODE="CGP"/>
</MSIGDB>
