• Jin-Yuan Shih, Meng-Feng Tsai, Tzu-Hua Chang, Yih-Leong Chang, Ang Yuan, Chong-Jen Yu, Shin-Bey Lin, Geou-Yarh Liou, Meng-Larn Lee, Jeremy J W Chen, Tse-Ming Hong, Shuenn-Chen Yang, Jen-Liang Su, Yung-Chie Lee, and Pan-Chyr Yang.
• Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
• Clin Cancer Res. 2005 Nov 15; 11 (22): 8070-8.

PurposeIn a previous genome-wide gene expression profiling analysis using an invasion cancer cell lines model, we have identified Slug as selectively overexpressed in the highly invasive cancer cells. Here, we investigated the clinical significance of Slug in lung adenocarcinoma and the role of Slug in the process of cancer cell invasion and metastasis.Experimental DesignReal-time quantitative reverse transcription-PCR was used to investigate Slug mRNA in surgically resected lung adenocarcinoma of 54 patients and its correlation with survival. We overexpressed Slug in a lung adenocarcinoma cell line with very low Slug levels and investigated the in vitro and in vivo effects of Slug expression.ResultsHigh expression of Slug mRNA in lung cancer tissue was significantly associated with postoperative relapse (P = 0.03) and shorter patient survival (P < 0.001). The overexpression of Slug enhanced xenograft tumor growth and increased microvessel counts in angiogenesis assay. Both inducible and constitutive overexpression of Slug suppressed the expression of E-cadherin and increased the in vitro invasive ability. Zymography revealed increased matrix metalloproteinase-2 activity in Slug overexpressed cells. ELISA, reverse transcription-PCR, and immunohistochemistry confirmed the increase of matrix metalloproteinase-2 proteins and mRNA in Slug overexpressed cells and xenograft tumors.ConclusionsSlug expression can predict the clinical outcome of lung adenocarcinoma patients. Slug is a novel invasion-promoting gene in lung adenocarcinoma.

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