RRC ID 67345
Author Katase N, Lefeuvre M, Tsujigiwa H, Fujii M, Ito S, Tamamura R, Buery RR, Gunduz M, Nagatsuka H.
Title Knockdown of Dkk-3 decreases cancer cell migration and invasion independently of the Wnt pathways in oral squamous cell carcinoma‑derived cells.
Journal Oncol Rep
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.
Volume 29(4)
Pages 1349-55
Published 2013-4-1
DOI 10.3892/or.2013.2251
PMID 23354949
MeSH Adaptor Proteins, Signal Transducing Adenocarcinoma / genetics Adenocarcinoma / metabolism Carcinoma, Squamous Cell / genetics* Carcinoma, Squamous Cell / pathology Cell Line, Tumor Cell Movement / genetics* Cell Proliferation Chemokines Gene Expression Regulation, Neoplastic Gene Knockdown Techniques Humans Intercellular Signaling Peptides and Proteins / genetics* Mouth Neoplasms / genetics* Mouth Neoplasms / pathology Neoplasm Invasiveness / genetics Neoplasm Invasiveness / pathology Signal Transduction Wnt Signaling Pathway / genetics
IF 3.417
Human and Animal Cells HSC-2(RCB1945) HSC-3(RCB1975) HSC-4(RCB1902) Ca9-22(RCB1976) Kato III(RCB2088) CW-2(RCB0778) COLO-320(RCB1193)