Wnt/β-catenin signaling regulates pathogenesis of human middle ear cholesteatoma

Cholesteatoma is characterized by the presence of a squamous epithelium invading the middle ear altering its growth properties. Wnt/beta-catenin signaling controls cell proliferation and differentiation by regulating expressions of target genes. Elevated levels of beta-catenin are related to tissue pathogenesis and tumor progression. Nevertheless, the mechanisms through which beta-catenin contributes to middle ear cholesteatoma development remain to be elucidated. We used proliferation assay, qRT-PCR assay, and western blotting to measure levels of the Wnt/beta-catenin signaling pathway. beta-Catenin expression evidently increased in middle ear cholesteatoma cells when compared with normal epithelial cells. Next, we found that treatment of Wnt inhibitor dickkopf1 (Dkk1) decreased beta-catenin expression, as well as the expression levels of cytokeratin 16 (CK16), CK18, Ki67 and PCNA. Overexpression of Wnt3a or beta-catenin induced the expression levels of CK16, CK18, Ki67 and PCNA. Furthermore, Dkk1 treatment significantly inhibited proliferation activity of middle ear cholesteatoma cells, whereas forced expression of Wnt3a or beta-catenin promoted proliferation activity of middle ear cholesteatoma cells. Wnt/beta-catenin signaling induced cell proliferation and up-regulated expressions of targeted genes in human middle ear cholesteatoma.