DKK3 Project

Aberrant activation of the Wnt signaling pathway is a major feature of many human cancers, including those of breast, colon, lung and bladder. Indeed, research in Wnt biology has recently provided evidence that the secreted Wnt antagonist Dickkopf-related protein 3 (Dkk-3) and its regulators may depict novel biomarker and therapeutic targets for some of the most important human tumor entities (reviewed in https://www.ncbi.nlm.nih.gov/pubmed/21982838).

Our research group recently found that abundant loss of DKK3 expression is detectable in the highly aggressive basal breast cancer subtype, this loss being significantly associated with reduced recurrence free survival (RFS) (Lorsy et al https://www.ncbi.nlm.nih.gov/pubmed/27467270). Functionally, DKK3 re-expression in human basal breast cancer cell lines led to suppression of cell growth possibly mediated by up-regulation of apoptosis. Moreover, ectopic DKK3 expression in mesenchymal basal breast cancer cells resulted in partial restoration of epithelial cell morphology which was molecularly supported by higher expression of epithelial markers like E-Cadherin and down-regulation of mesenchymal markers such as Snail1. Therefore, re-establishing Dkk-3 expression in cancer cells, especially basal-type breast cancer, may hold promise as novel targeted molecular tumor therapy.