Background: Dishevelled (Dvl) family proteins are cytoplasmic mediators of the Wnt/beta-catenin signaling pathway and have recently been linked to cancers. However, the roles of individual Dvls and their expression in human cancers are poorly defined. This work aimed to characterize the expression of Dvls and their correlation to clinicopathological factors and beta-catenin expression in non-small cell lung cancer (NSCLC).
Methods: We used immunohistochemistry to assess the presence of the three Dvl family proteins in 113 individual NSCLC specimens. Thirty-nine of the 113 cases were examined further for Dvl and beta-catenin protein expression in matched primary growths and autologous nodal metastases. We also examined the effect of Dvl-1 and Dvl-3 overexpression on beta-catenin expression and the invasive ability of A549 and QG56 lung cancer cells.
Results: The positive expression rate in primary tumors was 53.1% (60/113) for total Dvl, 36.3% (41/113) for Dvl-1, 36.3% (41/113) for Dvl-2 and 41.6% (47/113) for Dvl-3, while normal adult bronchial and alveolar epithelia showed negative expression of all these proteins. The expression levels of all three Dvl proteins were significantly higher in adenocarcinomas than in squamous carcinomas, and were associated with poor tumor differentiation. The positive expression of Dvl-1 and Dvl-2 proteins was correlated to advanced pTNM stages (III-IV vs. I-II). In addition, the expression levels of Dvl-1 and Dvl-3 were significantly higher in nodal metastases than in primary growths, with the Dvl-1 expression correlating to beta-catenin expression in the metastases. Exogenous expression of Dvl-1 and Dvl-3 both enhanced the invasive ability of A549 and QG56 cells, but had differential effects on beta-catenin protein expression in either cell line, without influencing beta-catenin mRNA levels.
Conclusions: Expression of Dvl family proteins, Dvl-1, Dvl-2 and Dvl-3, is common in NSCLCs. They may contribute to the progression of NSCLCs, but Dvl-1 and Dvl-3 may function on this process through different signaling pathways.