STANDARD_NAME	RODRIGUES_NTN1_TARGETS_UP
SYSTEMATIC_NAME	M12027
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/RODRIGUES_NTN1_TARGETS_UP
NAMESPACE	AFFY_HG_U133
DESCRIPTION_BRIEF	Genes up-regulated in HCT8/S11 cells (colon cancer) engineered to stably express NTN1 [GeneID=1630] off a plasmid vector.
DESCRIPTION_FULL	Deleted in colon cancer (DCC) and UNC5 function as netrin dependence receptors by inducing apoptosis in the absence of their ligand and accordingly were recently designated as putative conditional tumor suppressors. Herein, we determined whether netrin-1 and its receptors are implicated in cancer cell invasion and tumor progression. Expression of DCC, UNC5 and adenosine A2B-receptors (A2B-Rs) was investigated by reverse transcription polymerase chain reaction in human colon cancer cells. The impact of DCC restitution and netrin-1 was evaluated on collagen type I invasion, tumor growth and metastasis in nude mice, cancer cell survival and gene expression profiling. Flow cytometry, poly(ADP-ribose)polymerase-1 and caspase-8 activation were used to evaluate the impact of DCC on cell death. Both netrin-1 and A2B-R activation induced the invasive phenotype through the Rho-Rho kinase axis in DCC-deficient human colorectal cancer cells. Restitution of wild-type DCC blocked invasion induced by netrin-1, A2B-R agonist and other agents. Ectopic expression of netrin-1 led to increased growth of human colon tumor xenografts in athymic mice. Conversely, introduction of wt-DCC in kidney MDCKts.src-ggl cells strongly inhibited metastasis in lymph nodes and lungs and increased sensitivity to apoptosis in hypoxia. DNA microarrays revealed that netrin and DCC had common and divergent impacts on gene expression linked to cell cycle, survival, surface signaling and adhesion. Our findings underscore that netrin is a potent invasion and tumor growth-promoting agent and that DCC is a metastasis suppressor gene targeting both proinvasive and survival pathways in a cumulative manner.
PMID	17334389
GEOID	
AUTHORS	Rodrigues S,De Wever O,Bruyneel E,Rooney RJ,Gespach C
CONTRIBUTOR	Arthur Liberzon
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 3S: Direction=I
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	201311_s_at,201312_s_at,203372_s_at,203373_at,205795_at,206382_s_at,206470_at,207029_at,209290_s_at,210948_s_at,211124_s_at,212398_at,213032_at,213435_at,214774_x_at,215020_at,218980_at,219208_at,221606_s_at,226534_at,227332_at,229400_at,229649_at,231726_at
GENE_SYMBOLS	SH3BGRL,SH3BGRL,SOCS2,SOCS2,NRXN3,BDNF,PLXNC1,KITLG,NFIB,LEF1,KITLG,RDX,NFIB,SATB2,TOX3,NRXN3,FHOD3,FBXO11,HMGN5,KITLG,PXN-AS1,HOXD10,NRXN3,PCDHB14
FOUNDER_NAMES