Nr-CAM is a target gene of the β-catenin/LEF-1 pathway in melanoma and colon cancer and its expression enhances motility and confers tumorigenesis

Maralice E. Conacci-Sorrell, Tamar Ben-Yedidia, Michael Shtutman, Elena Feinstein, Paz Einat, Avri Ben-Ze'ev

Research output: Contribution to journalArticle

140 Scopus citations

Abstract

β-catenin and plakoglobin (γ-catenin) are homologous molecules involved in cell adhesion, linking cadherin receptors to the cytoskeleton. β-catenin is also a key component of the Wnt pathway by being a coactivator of LEF/TCF transcription factors. To identify novel target genes induced by β-catenin and/or plakoglobin, DNA microarray analysis was carried out with RNA from cells overexpressing either protein. This analysis revealed that Nr-CAM is the gene most extensively induced by both catenins. Overexpression of either β-catenin or plakoglobin induced Nr-CAM in a variety of cell types and the LEF/TCF binding sites in the Nr-CAM promoter were required for its activation by catenins. Retroviral transduction of Nr-CAM into NIH3T3 cells stimulated cell growth, enhanced motility, induced transformation, and produced rapidly growing tumors in nude mice. Nr-CAM and LEF-1 expression was elevated in human colon cancer tissue and cell lines and in human malignant melanoma cell lines but not in melanocytes or normal colon tissue. Dominant negative LEF-1 decreased Nr-CAM expression and antibodies to Nr-CAM inhibited the motility of B16 melanoma cells. The results indicate that induction of Nr-CAM transcription by β-catenin or plakoglobin plays a role in melanoma and colon cancer tumorigenesis, probably by promoting cell growth and motility.

Original languageEnglish (US)
Pages (from-to)2058-2072
Number of pages15
JournalGenes and Development
Volume16
Issue number16
DOIs
StatePublished - Aug 15 2002

Keywords

  • Carcinoma
  • Colon
  • Melanoma
  • Motility
  • Nr-CAM
  • Plakoglobin
  • β-catenin

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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