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

Chen,Ping; Zhao,Deshou; Sun,Yunwei; Huang,Liya; Zhang,Shuxian; Yuan,Yaozong

doi:10.3892/or.2012.2030

December 2012 Volume 28 Issue 6

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December 2012 Volume 28 Issue 6

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Article

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

Authors:
- Ping Chen
- Deshou Zhao
- Yunwei Sun
- Liya Huang
- Shuxian Zhang
- Yaozong Yuan
View Affiliations / Copyright

Affiliations: Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China, Department of Laboratory, Second Hospital Affiliated Lanzhou University, Lanzhou, Gansu 746000, P.R. China
Pages: 2149-2155
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Published online on: September 12, 2012

https://doi.org/10.3892/or.2012.2030
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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.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

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

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