Constitutive activation of Wnt/beta-catenin signaling pathway in migration-active melanoma cells: role of LEF-1 in melanoma with increased metastatic potential

Biochem Biophys Res Commun. 2001 Oct 19;288(1):8-15. doi: 10.1006/bbrc.2001.5719.


A constitutive complex of beta-catenin and LEF-1 has been detected in melanoma cell lines expressing either mutant beta-catenin or mutant APC (Rubinfeld et al., Science, 275, 1790-1792, 1997). However, it has been recently reported that beta-catenin mutations are rare in primary malignant melanoma, but its nuclear and/or cytoplasmic localization, a potential indicator of Wnt/beta-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 beta-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/beta-catenin signaling pathway in the tumor progression of malignant melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Movement*
  • Cell Nucleus / metabolism
  • Cytoskeletal Proteins / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Gene Expression Regulation, Neoplastic
  • Genes, Reporter
  • Humans
  • Lymphoid Enhancer-Binding Factor 1
  • 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 Proteins
  • Zebrafish Proteins*
  • beta Catenin


  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • LEF1 protein, human
  • Lymphoid Enhancer-Binding Factor 1
  • Proto-Oncogene Proteins
  • RNA, Neoplasm
  • Trans-Activators
  • Transcription Factors
  • Wnt Proteins
  • Zebrafish Proteins
  • beta Catenin