Tumor formation due to abnormalities in the β-catenin-independent pathway of Wnt signaling

Wnt signaling is a complex pathway in which beta-catenin is typically viewed as a central mediator in regulating cell proliferation and differentiation. The significance of Wnt signaling in human cancer has been elucidated by the identification of mutations in genes coding for the beta-catenin-dependent pathway components, adenomatous polyposis coli gene product, beta-catenin, and Axin. Within the past 15 years, evidence has been growing of a beta-catenin-independent pathway in Wnt signaling. It is likely that this pathway activates several intracellular signaling systems to regulate cell migration, adhesion, and polarity. The beta-catenin-independent pathway has also been shown to play an important role in tumor biology. In contrast to the beta-catenin-dependent pathway, which is upregulated in many cancers and serves as a tumor promoter, the role of the beta-catenin-independent pathway is still controversial. Here we review recent developments in both the functions and mechanisms of the beta-catenin-independent pathway, with an emphasis on its functional contribution to human tumor progression.