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.
Highlights
Oral squamous cell carcinoma (OSCC) accounts for 5% of all cancers in men and 2% in women [1]
Due to the possible oncogenic function of Dkk-3, in the present study we investigated the mRNA expression of Dkk‐3 in OSCC cell lines, and observed the effects of Dkk-3 knockdown by RNA interference on cell proliferation, migration and invasion
Among the OSCC cell lines, Dkk-3 mRNA expression was comparatively high in the Ca9-22 cells and that of HSC4 was comparatively low
Summary
Oral squamous cell carcinoma (OSCC) accounts for 5% of all cancers in men and 2% in women [1]. The Dkk-3 protein was dominantly expressed in SCC tissue and cell lines, and patients without Dkk-3 protein expression did not undergo metastasis but exhibited prolonged survival [10]. Following the various Dkk-3 expression patterns in normal, dysplastic and SCC tissue, Dkk-3 protein expression was found to be increased accompanied by cancer progression [11]. All of these findings strongly suggest the oncogenic function of Dkk-3. Due to the possible oncogenic function of Dkk-3, in the present study we investigated the mRNA expression of Dkk‐3 in OSCC cell lines, and observed the effects of Dkk-3 knockdown by RNA interference on cell proliferation, migration and invasion
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
