STANDARD_NAME	ZHU_SKIL_TARGETS_UP
SYSTEMATIC_NAME	M2273
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/ZHU_SKIL_TARGETS_UP
NAMESPACE	HUMAN_GENE_SYMBOL
DESCRIPTION_BRIEF	Genes up-regulated in A549 cells (lung adenocarcinoma) upon SKIL [GeneID=6498] knockdown by RNAi.
DESCRIPTION_FULL	SnoN is an important negative regulator of transforming growth factor beta signaling through its ability to interact with and repress the activity of Smad proteins. It was originally identified as an oncoprotein based on its ability to induce anchorage-independent growth in chicken embryo fibroblasts. However, the roles of SnoN in mammalian epithelial carcinogenesis have not been well defined. Here we show for the first time that SnoN plays an important but complex role in human cancer. SnoN expression is highly elevated in many human cancer cell lines, and this high level of SnoN promotes mitogenic transformation of breast and lung cancer cell lines in vitro and tumor growth in vivo, consistent with its proposed pro-oncogenic role. However, this high level of SnoN expression also inhibits epithelial-to-mesenchymal transdifferentiation. Breast and lung cancer cells expressing the shRNA for SnoN exhibited an increase in cell motility, actin stress fiber formation, metalloprotease activity, and extracellular matrix production as well as a reduction in adherens junction proteins. Supporting this observation, in an in vivo breast cancer metastasis model, reducing SnoN expression was found to moderately enhance metastasis of human breast cancer cells to bone and lung. Thus, SnoN plays both pro-tumorigenic and antitumorigenic roles at different stages of mammalian malignant progression. The growth-promoting activity of SnoN appears to require its ability to bind to and repress the Smad proteins, while the antitumorigenic activity can be mediated by both Smad-dependent and Smad-independent pathways and requires the activity of small GTPase RhoA. Our study has established the importance of SnoN in mammalian epithelial carcinogenesis and revealed a novel aspect of SnoN function in malignant progression.
PMID	17074815
GEOID	
AUTHORS	Zhu Q,Krakowski AR,Dunham EE,Wang L,Bandyopadhyay A,Berdeaux R,Martin GS,Sun L,Luo K
CONTRIBUTOR	Arthur Liberzon
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 2: Regulation=Up
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	CCNG2,CDKN1A,DCN,ECM2,EGFR,ENPP2,FN1,GADD34,GADD45A,IGFBP1,ITGA2,JUNB,MMP16,ORP150,PLAU,SEL1L,SERPINE1,ST5,TC10,VEGF
GENE_SYMBOLS	CCNG2,CDKN1A,DCN,ECM2,EGFR,ENPP2,FN1,PPP1R15A,GADD45A,IGFBP1,ITGA2,JUNB,MMP16,HYOU1,PLAU,SEL1L,SERPINE1,DENND2B,RHOQ,VEGFA
FOUNDER_NAMES