Wnt signaling and cancer development: therapeutic implication
Abstract:
Wnt proteins are a large family of secreted glycoproteins that activate signal transduction pathways to control a wide variety of cellular processes such as determination of cell fate, proliferation, migration, and polarity. Wnts are capable of signaling through several pathways, the best-characterized being the canonical beta-catenin/Tcf-mediated pathway. Canonical Wnts stabilize β-catenin protein, which has implications in the genesis of many human cancers like non-small cell lung cancer, colorectal carcinoma, prostate cancer, breast cancer and many others. In all of these cancers the common denominator is the activation of target genes. Although detailed mechanisms are not well understood of why Wnts are overexpressed in one tumor and down regulated in another, the pleiotropism of Wnt signaling is evident. The pathway itself offers ample targeting nodal points for cancer drug development. The identification of many important regulatory genes and the mechanism of their function offer an opportunity to develop new therapies targeting this pathway. In this review, we describe the roles of several oncogenes of the Wnt/β-catenin signaling pathway in the development of tumorigenesis and discuss few strategies that are already developed or can be explored to target key components of the Wnt/ β-catenin signaling pathway in finding of anti-cancer drugs.