Silencing of Wwox Increases Nuclear Import of Dvl proteins in Head and Neck Cancer

Background: Wnt signaling pathway is associated with a variety of human cancers, including HNSCC. Wnt proteins control cellular events such as proliferation, fate specification, polarity, and migration by transducing signals to the nucleus through several cytoplasmic relay proteins. Although activation of the Wnt/β-catenin pathway is a frequent event in various cancers, there is limited knowledge on the contribution of this signaling mechanism in HNSCC. The Wwox tumor suppressor protein participates in the regulation of Wnt signaling by interacting with Dvl proteins. Methods: In this study, we used qRT-PCR and western blotting to examine the mRNA and protein levels of the Dvls in association with WWOX in HNSCC cell lines and tumor tissues. Results: We found that silencing of WWOX leads to increased nuclear localization of the Dvl proteins in cell lines. However, we detected an increase only in the nuclear localization of Dvl-1 in tumor tissues. Conclusions: Our results suggest that aberrant WWOX expression contributes to HNSCC through the Wnt signaling pathway. Decreased expression of WWOX may function in HNSCC progression by allowing the nuclear localization of Dvl proteins.