Gene Set: LE_SKI_TARGETS_UP

Standard name LE_SKI_TARGETS_UP
Systematic name M362
Brief description Selected genes implicated in metastasis and epithelial-to-mesenchymal transition (EMT) which were up-regulated in MDA-MB-231 cells (breast cancer) upon knockdown of SKI [GeneID=6497] by RNAi.
Full description or abstract 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.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 18451154   Authors: Le Scolan E,Zhu Q,Wang L,Bandyopadhyay A,Javelaud D,Mauviel A,Sun L,Luo K
Exact source Table 1S
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Organism Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
Source platform HUMAN_GENE_SYMBOL
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Version history 3.0: First introduced

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