Journal Article

Dual role of <i>Ski</i> in pancreatic cancer cells: tumor-promoting versus metastasis-suppressive function

Peng Wang, Zhen Chen, Zhi-Qiang Meng, Jie Fan, Jian-Min Luo, Wang Liang, Jun-Hua Lin, Zhen-Hua Zhou, Hao Chen, Kun Wang, Ye-Hua Shen, Zu-De Xu and Lu-Ming Liu

in Carcinogenesis

Volume 30, issue 9, pages 1497-1506
Published in print September 2009 | ISSN: 0143-3334
Published online June 2009 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgp154
Dual role of Ski in pancreatic cancer cells: tumor-promoting versus metastasis-suppressive function

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Ski used to be defined as an oncogene that contributes to the resistance of tumor cells to transforming growth factor-β (TGF-β)-induced growth arrest. As TGF-β has a dual effect on tumor growth with both tumor-suppressing and -promoting activity depending on the stage of carcinogenesis and the cell type, the precise role of Ski in carcinogenesis remains unclear. In this study, we show that downregulation of Ski through lentivirus-mediated RNA interference decreases tumor growth both in vitro and in vivo, yet promotes cell invasiveness in vitro, and lung metastasis in vivo in the pancreatic cancer cell line SW1990, which contain wild-type Smad4 expression, and the BxPC3 cell line, which is Smad4 deficient. We also show that the downregulation of Ski increases TGF-β-induced transcriptional activity, which is associated with increased TGF-β-dependent Smad2/3 phosphorylation, and results in an altered expression profile of TGF-β-inducible genes involved in metastasis, angiogenesis and cell proliferation and epithelial–mesenchymal transition. Immunohistochemical analysis of specimens from 71 patients with pancreatic adenocarcinoma showed a significant association between overexpression of Ski and decreased patient survival time (P = 0.0024). Our results suggest that Ski may act as a tumor proliferation-promoting factor or as a metastatic suppressor in human pancreatic cancer.

Journal Article.  5627 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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