Bypassing melanocyte senescence by ß-catenin: A novel way to promote melanoma

Abstract

The Wnt/ß-catenin signaling pathway plays a key role in several cellular functions during embryonic development and adult homeostasis. The deregulation of this pathway may lead to the development of cancer, including melanoma. Deregulation of the Wnt/ß-catenin pathway occurs through either the induction/repression of, or specific mutations in, various members of this signaling pathway; this results in the stabilization of ß-catenin and its translocation from the cytoplasm to the nucleus, where it regulates transcription. Although nuclear ß-catenin is clearly involved in malignant transformation, the mechanism by which it exerts its effects remains elusive. This review focuses on the molecular and cellular mechanisms that are driven by ß-catenin and lead to melanocyte transformation. In particular, we describe how ß-catenin induces melanocyte immortalization, a novel activity of this multifunction protein. Finally, we discuss how ß-catenin-induced immortalization can cooperate with MAPKinase pathways to produce melanoma. © 2008 Elsevier Masson SAS. All rights reserved.