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Oncol Rep. 29(4):1349-55. 2013. doi: 10.3892/or.2013.2251.  

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

Katase NLefeuvre MTsujigiwa HFujii MIto STamamura RBuery RRGunduz MNagatsuka H.


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.



結果:DKK3をsiRNAでノックダウンするとWnt signalとは別の機序で腫瘍細胞の浸潤・遊走が低下する。


前回の論文(Katase N et al. Oncol Lett. 2012)では、HNSCCでは他の癌とは異なり、DKK3タンパクがほとんどの症例で発現しており、




(1)siRNAの導入によるDKK3 mRNA発現低下


 トランスフェクションし、DKK3 mRNA発現が低下することを確認した。








(3)DKK3ノックダウンはWnt signalには影響しない

  Western blottingではWnt canonical pathway、non-canonical pathwayともに

  変化がなく、DKK3ノックダウンによる遊走、浸潤の低下はWnt signal以外の



ノックダウンすると、Wnt signalとは無関係の機序で腫瘍の浸潤と遊走が


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