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