title: Protein inhibitor of activated STAT-1 is downregulated in gastric cancer             tissue and involved in cell metastasis.
abstract: Protein inhibitor of activated STAT-1 (PIAS1) is a novel modulator of the             JAK/STAT signaling pathway that negatively regulates the inflammatory response.             It has been also reported to be downregulated in a variety of human cancer cell             lines. However, the role of PIAS1 in gastric cancer remains unclear. In this study,             we investigated the prognostic value of PIAS1 expression and its regulated mechanisms             in gastric cancer cell metastasis. Therefore, the expression of PIASI was explored             in gastric cancer tissues and adjacent tissues of gastric cancer with 31 cases             of patients, and the prognostic value was analyzed. In addition, the growth and             invasion in SGC7901 cells were investigated in the restoration of PIAS1 expression             with Ad5/F35-PIAS1 or Ad5/F35-vector or PBS treatment, and the activity of P38MAPK,             P-P38MAPK, JNK/SAPK, P-JNK/SAPK, ERK and P-ERK, were detected by western blotting.             The tumor migratory factors MMP-9, MMP-2 and ICAM-1 were analyzed by western blotting.             The results demonstrated that 22 of 31 (70.9%) gastric cancer specimens showed             low levels of PIAS1 expression from immunohistochemistry staining using tissue             microarrays. Statistical analysis suggested that the downregulation of PIAS1 was             significantly correlated with tumor staging. Furthermore, we found that the restoration             of PIAS1 expression mediated by Ad5/F35 virus suppressed cell proliferation and             invasion accompanied by the inhibition of P38MAPK and ERK protein expression and             activity, but not JNK/SAPK protein. Notably, PIAS1 restoration with the transfection             of Ad5/F35-PIAS1 robustly decreased the expression of tumor migratory factors             including MMP-9, MMP-2 and ICAM-1 compared to Ad5/F35-vector. These data suggest             that PIAS1 may function as a tumor suppressor to regulate gastric cancer cell             metastasis by targeting the MAPK signaling pathway.
authors.affiliation: Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Deshou
authors.initials: D
authors.lastname: Zhao
authors.forename: Yunwei
authors.initials: Y
authors.lastname: Sun
authors.forename: Liya
authors.initials: L
authors.lastname: Huang
authors.forename: Shuxian
authors.initials: S
authors.lastname: Zhang
authors.forename: Yaozong
authors.initials: Y
authors.lastname: Yuan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics*; D050828:Protein Inhibitors of Activated STAT / Q000235:genetics / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C573420:ICAM1 protein, human; C106529:PIAS1 protein, human; D050828:Protein Inhibitors of Activated STAT; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D018799:Intercellular Adhesion Molecule-1; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9