Protein inhibitor of activated STAT-1 is downregulated in gastric cancer tissue and involved in cell metastasis

Oncol Rep. 2012 Dec;28(6):2149-55. doi: 10.3892/or.2012.2030. Epub 2012 Sep 12.

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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Humans
  • Inflammation / immunology
  • Inflammation / metabolism
  • Intercellular Adhesion Molecule-1 / metabolism
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • MAP Kinase Signaling System*
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Metastasis / genetics*
  • Protein Inhibitors of Activated STAT / genetics
  • Protein Inhibitors of Activated STAT / metabolism*
  • STAT1 Transcription Factor / metabolism
  • Small Ubiquitin-Related Modifier Proteins / genetics
  • Small Ubiquitin-Related Modifier Proteins / metabolism*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Young Adult
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Biomarkers, Tumor
  • ICAM1 protein, human
  • PIAS1 protein, human
  • Protein Inhibitors of Activated STAT
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Small Ubiquitin-Related Modifier Proteins
  • Intercellular Adhesion Molecule-1
  • Extracellular Signal-Regulated MAP Kinases
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9