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Upregulated, 7q21-22 amplicon candidate gene SHFM1 confers oncogenic advantage by suppressing p53 function in gastric cancer

 Sembulingam Tamilzhalagan  ;  Muthulakshmi Muthuswami  ;  Jayaprakash Periasamy  ;  Ming Hui Lee  ;  Sun Young Rha  ;  Patrick Tan  ;  Kumaresan Ganesan 
 CELLULAR SIGNALLING, Vol.27(6) : 1075-1086, 2015 
Journal Title
Issue Date
Chromosomes, Human, Pair 7* ; G2 Phase Cell Cycle Checkpoints ; Gene Expression Regulation, Neoplastic ; Humans ; M Phase Cell Cycle Checkpoints ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphorylation ; Proteasome Endopeptidase Complex/chemistry ; Proteasome Endopeptidase Complex/genetics ; Proteasome Endopeptidase Complex/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism ; RNA Interference ; RNA, Small Interfering/metabolism ; Stomach Neoplasms/genetics ; Stomach Neoplasms/metabolism* ; Stomach Neoplasms/pathology ; Transcriptional Activation ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism* ; Ubiquitin/metabolism ; Up-Regulation ; src-Family Kinases/metabolism
7q21.12–22.3 ; Gastric cancer ; Genomic amplification ; SHFM1 ; SNP array ; p53 pathway
Chromosomal aberrations are hallmarks of cancers and the locus of frequent genomic amplifications often harbors key cancer driver genes. Many genomic amplicons remain larger with hundreds of genes and the key drivers remain to be identified by an amplification-wide systematic analysis. The 7q21.12-q22.3 genomic amplification is frequent in gastric cancers which occur in ~10% of the patients and multiple cell lines. This 7q21.12-q22.3 amplicon has not yet been completely analyzed towards identifying the driver genes and their functional contribution in oncogenesis. The amplitude and prevalence indicate the important role conferred by this amplicon in gastric cancers. Among the 159 genes of this amplicon, 12 genes are found over-expressed in primary gastric tumors and cell lines. Many of the over-expressed genes show negative association with p53 transcriptional activity. RNAi based functional screening of the genes reveal, SHFM1 as key gastric cancer driver gene. SHFM1 confers cell cycle progression and resistance to p53 stabilizing drugs in gastric cancer cells. SHFM1 also activates Src, MAPK/ERK and PI3K/Akt signaling pathways. This is the first integrative genomic investigation of 7q21.12-q22.3 amplicon revealing the potential oncogenic candidacy of 12 genes. The oncogenic contribution of SHFM1, mediated by the p53 suppressive feature has been demonstrated in gastric cancer cells.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
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