Dickkopf-1 in human oral cancer

Dickkopf-1 (Dkkl), a negative regulator of the Wnt signaling pathway, is implicated in tumorigenesis in several types of cancer. The purpose of this study was to determine the involvement of Dkk1 in oral squamous cell carcinoma (OSCC). We found that Dkk1 is frequently upregulated in OSCC-derived cell lines and primary OSCCs compared with normal counterparts. Unexpectedly, Dkkl-positive cases were correlated significantly (P<0.05) with a low risk of regional lymph node metastasis. We also found that cellular migration and invasiveness increased in Dkkl knockdown cells and decreased in Dkkl overexpressed cells. Furthermore, we investigated the relationship between the expression of Dkkl and distribution of β-catenin in OSCC cells, since the Wnt signaling pathway is related closely to β-catenin. Whereas alteration of the β-catenin levels was not observed in each subcellular fractionation, the phosphorylated β-catenin levels in nuclei increased in Dkkl knockdown cells and decreased in Dkkl overexpressed cells. These data indicated that the high phosphorylation level of β-catenin in nuclei was correlated with a high risk of tumor invasiveness. The current study suggested that Dkkl plays an important role in regulating cellular migration and invasiveness, making Dkkl a potential biomarker for early detection of lymph node metastasis in OSCCs.