STANDARD_NAME LE_SKI_TARGETS_DN SYSTEMATIC_NAME M15687 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/LE_SKI_TARGETS_DN NAMESPACE HUMAN_GENE_SYMBOL DESCRIPTION_BRIEF Selected genes implicated in metastasis and epithelial-to-mesenchymal transition (EMT) which were down-regulated in MDA-MB-231 cells (breast cancer) upon knockdown of SKI [GeneID=6497] by RNAi. DESCRIPTION_FULL c-Ski is an important corepressor of transforming growth factor-beta (TGF-beta) signaling through its ability to bind to and repress the activity of the Smad proteins. It was initially identified as an oncogene that promotes anchorage-independent growth of chicken and quail embryo fibroblasts when overexpressed. Although increased Ski expression is detected in many human cancer cells, the roles of Ski in mammalian carcinogenesis have yet to be defined. Here, we report that reducing Ski expression in breast and lung cancer cells does not affect tumor growth but enhances tumor metastasis in vivo. Thus, in these cells, Ski plays an antitumorigenic role. We also showed that TGF-beta, a cytokine that is often highly expressed in metastatic tumors, induces Ski degradation through the ubiquitin-dependent proteasome in malignant human cancer cells. On TGF-beta treatment, the E3 ubiquitin ligase Arkadia mediates degradation of Ski in a Smad-dependent manner. Although Arkadia interacts with Ski in the absence of TGF-beta, binding of phosphorylated Smad2 or Smad3 to Ski is required to induce efficient degradation of Ski by Arkadia. Our results suggest that the ability of TGF-beta to induce degradation of Ski could be an additional mechanism contributing to its protumorigenic activity. PMID 18451154 GEOID AUTHORS Le Scolan E,Zhu Q,Wang L,Bandyopadhyay A,Javelaud D,Mauviel A,Sun L,Luo K CONTRIBUTOR Jessica Robertson CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Table 1S FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS COL18A1,DLX4,FBLN3,FHL1,ID4,KISS-1,SOCS2,TFPI2,Timp-3 GENE_SYMBOLS COL18A1,DLX4,EFEMP1,FHL1,ID4,,SOCS2,TFPI2, FOUNDER_NAMES