Knockdown of Dkk-3 decreases cancer cell migration and invasion independently             of the Wnt pathways in oral squamous cell carcinoma‑derived cells.
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.
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
Naoki
N
Katase
Mathieu
M
Lefeuvre
Hidetsugu
H
Tsujigiwa
Masae
M
Fujii
Satoshi
S
Ito
Ryo
R
Tamamura
Rosario Rivera
RR
Buery
Mehmet
M
Gunduz
Hitoshi
H
Nagatsuka
D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D018925:Chemokines; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D015398:Signal Transduction; D060449:Wnt Signaling Pathway / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D018925:Chemokines; C498624:DKK3 protein, human; D036341:Intercellular Signaling Peptides and Proteins