Constitutive Activation of Wnt/β-Catenin Signaling Pathway in Migration-Active Melanoma Cells: Role of LEF-1 in Melanoma with Increased Metastatic Potential

• Published in: Biochemical and biophysical research communications 2001-10, Vol.288 (1), p.8-15
• Main Authors: Murakami, Takashi, Toda, Sunao, Fujimoto, Mitsuo, Ohtsuki, Mamitaro, Byers, H.Randolph, Etoh, Takafumi, Nakagawa, Hidemi
• Format: Article
• Language: English
• Subjects: b-catenin; beta Catenin; cell motility; Cell Movement; Cell Nucleus - metabolism; Cytoskeletal Proteins - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Gene Expression Regulation, Neoplastic; Genes, Reporter; Humans; LEF-1; LEF-1 protein; Lymphoid Enhancer-Binding Factor 1; melanoma; Melanoma - genetics; Melanoma - metabolism; Melanoma - pathology; Mutation; Neoplasm Metastasis; Proto-Oncogene Proteins - physiology; RNA, Neoplasm - biosynthesis; Signal Transduction; Trans-Activators; Transcription Factors - genetics; Transcription Factors - physiology; Transcriptional Activation; Tumor Cells, Cultured; Wnt; Wnt gene; Wnt protein; Wnt Proteins; Zebrafish Proteins; β-catenin
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.2001.5719

A constitutive complex of β-catenin and LEF-1 has been detected in melanoma cell lines expressing either mutant β-catenin or mutant APC (Rubinfeld et al., Science, 275, 1790–1792, 1997). However, it has been recently reported that β-catenin mutations are rare in primary malignant melanoma, but its nuclear and/or cytoplasmic localization, a potential indicator of Wnt/β-catenin pathway activation, is frequently observed in melanoma (Rimm et al., Am. J. Pathol., 154, 325–329, 1999). In human malignant melanoma, the appearance of the tumorigenic phase represents a capacity for metastasis and is the significant phenotypic step in disease progression. Cell motility in invasive melanoma is thought to play a crucial role in metastatic behavior. In this work, we sought to determine which transcription factor of the LEF/TCF family was preferentially involved in human melanoma from different stages of tumor progression. We show that LEF-1 mRNA expression is predominant in highly migrating cells from metastatic melanomas. These actively migrating melanoma cells showed nuclear and cytoplasmic accumulation of β-catenin and active transcription from a reporter plasmid of the LEF/TCF binding site. These results may provide a new insight into the role of the Wnt/β-catenin signaling pathway in the tumor progression of malignant melanoma.