Knockdown of Dkk-3 decreases cancer cell migration and invasion independently of the Wnt pathways in oral squamous cell carcinoma‑derived cells.

Oncol Rep. 2013 Apr;29(4):1349-55.

Katase N, Lefeuvre M, Tsujigiwa H, Fujii M, Ito S, Tamamura R, Buery RR, Gunduz M, Nagatsuka H.

Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. katase-n@cc.okayama-u.ac.jp

Abstract

Oral squamous cell carcinoma (OSCC) is thought to arise as the result of cumulative genetic or epigenetic alterations in cancer-associated genes. We focused on the Dickkopf-3 (Dkk-3) gene as a candidate tumor suppressor in OSCC. Dkk-3 is a potential tumor suppressor, and its downregulation has been reported in various types of malignancies. However, our previous data demonstrated that the Dkk-3 protein was dominantly expressed in OSCC tissue, and its expression was correlated with a high incidence of metastasis and with poor prognosis. In order to explain this paradox, we performed functional analyses of the Dkk-3 gene in cancer cell lines. RT-PCR revealed that Dkk-3 mRNA expression was observed in OSCC-derived cell lines but not in gastrointestinal or colorectal adenocarcinoma‑derived cell lines. The siRNA for Dkk-3 was transfected into Dkk-3-expressing cells, and the changes in cell proliferation, invasion and migration were assessed. The knockdown of Dkk-3 mRNA by siRNA transfection did not affect cell proliferation, but it significantly decreased cell migration and invasion. To further investigate the precise mechanism that contributes to the potential oncogenic function of Dkk-3, the Wnt canonical pathway and non-canonical pathways were assessed. Western blotting demonstrated that the effect of Dkk-3 knockdown on cell migration or invasion was not caused by activation of the Wnt pathways. These data demonstrated that Dkk-3 expression in OSCC was different than that in adenocarcinomas. Dkk-3 may possess an oncogenic function that is independent of Wnt signaling.

PMID: 23354949

 

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