
doi: 10.2741/1831
pmid: 16146765
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.
Cell Nucleus, Homeodomain Proteins, Cytoplasm, Microphthalmia-Associated Transcription Factor, Transcription, Genetic, Cell Membrane, Cell Differentiation, Intramolecular Oxidoreductases, Cell Movement, Neural Crest, POU Domain Factors, Hepatocytes, Humans, Melanocytes, Cell Lineage, Cyclin D1, Cell Adhesion Molecules, Melanoma, Cell Proliferation, Signal Transduction
Cell Nucleus, Homeodomain Proteins, Cytoplasm, Microphthalmia-Associated Transcription Factor, Transcription, Genetic, Cell Membrane, Cell Differentiation, Intramolecular Oxidoreductases, Cell Movement, Neural Crest, POU Domain Factors, Hepatocytes, Humans, Melanocytes, Cell Lineage, Cyclin D1, Cell Adhesion Molecules, Melanoma, Cell Proliferation, Signal Transduction
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