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

Wnt signaling is a complex pathway in which β‐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 β‐catenin‐dependent pathway components, adenomatous polyposis coli gene product, β‐catenin, and Axin. Within the past 15 years, evidence has been growing of a β‐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 β‐catenin‐independent pathway has also been shown to play an important role in tumor biology. In contrast to the β‐catenin‐dependent pathway, which is upregulated in many cancers and serves as a tumor promoter, the role of the β‐catenin‐independent pathway is still controversial. Here we review recent developments in both the functions and mechanisms of the β‐catenin‐independent pathway, with an emphasis on its functional contribution to human tumor progression. (Cancer Sci 2008; 99: 202–208)