STANDARD_NAME ITO_PTTG1_TARGETS_UP SYSTEMATIC_NAME M2282 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/ITO_PTTG1_TARGETS_UP NAMESPACE Human_RefSeq DESCRIPTION_BRIEF Genes up-regulated in HSA/c and KYSE140 cells (esophageal squamous cell carcinoma, ESCC) after knockdown of PTTG1 [GeneID=9232] by RNAi. DESCRIPTION_FULL Human pituitary tumor-transforming 1 (PTTG1)/securin is a putative oncoprotein that is overexpressed in various tumor types. However, the involvement of PTTG1 in gastrointestinal cancer development and progression remains unclear. In this study, we investigated the clinical significance and biological effects of PTTG1 in esophageal squamous cell carcinoma (ESCC). Immunohistochemical studies performed on 113 primary ESCC specimens revealed a high prevalence of PTTG1 overexpression (60.2%), which was significantly associated with lymph node metastasis (regional, P = 0.042; distant, P = 0.005), advanced tumor stage (P = 0.028), and poorer overall survival (P = 0.017, log-rank test; P = 0.044, Cox proportional hazard model). Eleven ESCC cell lines expressed PTTG1 protein at levels 2.4 to 6.6 times higher than those in normal esophageal epithelial cells (HEEpiC). PTTG1 protein expression was confined to the nucleus in HEEpiC cells but present in both the cytoplasm and nucleus in ESCC cells. Two small interfering RNAs (siRNA) inhibited PTTG1 mRNA and protein expression in three ESCC cell lines by 77% to 97%. In addition, PTTG1 down-regulation by these siRNAs significantly reduced cell motility in all three ESCC cell lines (P < 0.01) in vitro, as well as popliteal lymph node metastases of ESCC cells in nude mice (P = 0.020). Global gene expression profiling suggested that several members of the Ras and Rho gene families, including RRAS, RHOG, ARHGAP1, and ARHGADIA, represented potential downstream genes in the PTTG1 pathway. Taken together, these findings suggest that PTTG1 overexpression promotes cell motility and lymph node metastasis in ESCC patients, leading to poorer survival. Thus, PTTG1 constitutes a potential biomarker and therapeutic target in ESCCs with lymph node metastases. PMID 18451147 GEOID GSE7447 AUTHORS Ito T,Shimada Y,Kan T,David S,Cheng Y,Mori Y,Agarwal R,Paun B,Jin Z,Olaru A,Hamilton JP,Yang J,Abraham JM,Meltzer SJ,Sato F CONTRIBUTOR Jessica Robertson CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Table 3: Up-regulated genes FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS NM_001005340,NM_001072,NM_001219,NM_001498,NM_001627,NM_003246,NM_003739,NM_003932,NM_004887,NM_006931,NM_013253,NM_019558,NM_205862 GENE_SYMBOLS GPNMB,UGT1A6,CALU,GCLC,ALCAM,THBS1,AKR1C3,ST13,CXCL14,SLC2A3,DKK3,HOXD8,UGT1A6 FOUNDER_NAMES