STANDARD_NAME	JIANG_TIP30_TARGETS_DN
SYSTEMATIC_NAME	M13930
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/JIANG_TIP30_TARGETS_DN
NAMESPACE	Human_RefSeq
DESCRIPTION_BRIEF	Down-regulated genes in HepG2 cells (liver cancer) overexpressing an oncogenic variant of tumor suppressor TIP30 [GeneID=10553] compared to its wild type form.
DESCRIPTION_FULL	TIP30 is a tumor suppressor whose expression is altered in human liver, prostate, lung, colon, and breast cancers. Mice lacking TIP30 spontaneously developed hepatocellular carcinomas (HCC) and other tumors at a higher incidence than wild-type mice. Somatic missense mutations in the TIP30 gene were identified in human HCC tissue specimens, which resulted in instability or abnormal cellular distribution of TIP30 protein in cells. Here, we show that TIP30 mutants are able to promote cell growth and invasion and inhibit cisplatin-induced apoptosis in the HCC cell line HepG2 negative for endogenous TIP30. Moreover, one of the TIP30 mutants can dramatically accelerate tumor formation in immunodeficient mice. Analysis of gene expression in HepG2 cells, ectopically expressing either wild-type TIP30 or mutant TIP30, by Affymetrix GeneChip array, real-time quantitative PCR, and Western blotting assays reveals that TIP30 mutants can alter expression of genes involved in the regulation of tumorigenesis. This includes up-regulation of expression of N-cadherin and c-MYC and down-regulation of expression of p53 and E-cadherin. N-cadherin knockdown with small interfering RNA in HepG2 cells expressing mutant TIP30 resulted in a profound reduction in cell viability. Taken together, our data indicate that somatic mutations in the TIP30 gene may abolish its native tumor-suppressor activity and gain oncogenic activities partially through up-regulation of N-cadherin, thereby potentiating the pathogenesis of HCC in patients.
PMID	17440068
GEOID	
AUTHORS	Jiang C,Pecha J,Hoshino I,Ankrapp D,Xiao H
CONTRIBUTOR	Jessica Robertson
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 1S: Fold change < -1.7
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	NM_000546,NM_000612,NM_001909,NM_002011,NM_002383,NM_002567,NM_003461,NM_003488,NM_003655,NM_004309,NM_004343,NM_005558,NM_006640,NM_006698,NM_007144,NM_011602,NM_012151,NM_014003,NM_014430,NM_016180,NM_016333,NM_021195,NM_054012,NM_080792
GENE_SYMBOLS	TP53,IGF2,CTSD,FGFR4,MAZ,PEBP1,ZYX,AKAP1,CBX4,ARHGDIA,CALR,LAD1,SEPTIN9,BLCAP,PCGF2,TLN1,F8A1,DHX38,CIDEB,SLC45A2,SRRM2,CLDN6,ASS1,SIRPA
FOUNDER_NAMES