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

Abstract

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.

Determination of WWOX Function in Modulating Cellular Pathways Activated by AP-2α and AP-2γ Transcription Factors in Bladder Cancer

“…The identification of AP-2 targets and their functional annotation provided an insight into the signaling pathways in which they are involved. The data on the role of WWOX, AP-2α and AP-2γ in the regulation of MAPK [22][23][24], Wnt [25][26][27], Ras [28][29][30] and PI3K-Akt [31][32][33] signaling are available; however, no influence on Rap1 signaling was found in the literature, suggesting that these could be novel observations. Aside from signal transduction, WWOX and two AP-2 factors are implicated in adhesion [34][35][36], migration [24,37,38], axon guidance (indirectly) [39][40][41] and regulation of extracellular matrix [42][43][44] or miRNA [45,46].…”

“…The identification of AP-2 targets and their functional annotation provided an insight into the signaling pathways in which they are involved. The data on the role of WWOX, AP-2α and AP-2γ in the regulation of MAPK [22][23][24], Wnt [25][26][27], Ras [28][29][30] and PI3K-…”

Dishevelled localization and function are differentially regulated by structurally distinct sterols

“…Sterol regulated association of Tp53 with DVL2 may play a role in Tp53 tumor suppressor activity. It has been shown that silencing of the Wwox tumor suppressor increases nuclear DVL2 in head and neck cancer (Celebi et al, 2020). We also observed significant overlap between DVL2 and p53 interacting protein networks ( Figure 6C ).…”