The WNT/Beta-catenin pathway in melanoma.

The Wnt/beta-catenin pathway is involved in various cellular activities--including determination, proliferation, migration and differentiation--in embryonic development and adult homeostasis. The deregulation or constitutive activation of the Wnt/beta-catenin pathway may lead to cancer formation. This review focuses on the role of the Wnt/beta-catenin canonical signaling pathway in the melanocyte lineage, and more specifically, in melanoma. Several components of the Wnt/beta-catenin pathway, such as APC, ICAT, LEF1 and beta-catenin are modified in melanoma tumors and cell lines, leading to activation of this signaling. A hallmark of the activation of this pathway is the presence of beta-catenin in the nucleus. Indeed, beta-catenin is found in about 30% of human melanoma nuclei, indicating a potentially specific role for this signaling pathway in this aggressive type of cancer. Beta-catenin can induce ubiquitous genes such as myc or cyclinD1, cell lineage-restricted genes such as Brn2 and melanocyte-specific genes such as Mitf-M and Dct. The Mitf-M and Brn-2 genes encode transcription factors. Mitf plays a critical role in melanocyte survival, proliferation and differentiation. Brn-2 is involved in melanoma proliferation. Determining how the Wnt/beta-catenin signaling pathway, alone or with other pathways, orchestrates the induction of target genes involved in a diverse range of activities represents a major challenge in research into melanoma formation and tumor progression.