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

138 Citations (Scopus)

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

Fingerprint

Catenins
Colonic Neoplasms
Melanoma
gamma Catenin
Carcinogenesis
Genes
TCF Transcription Factors
Cell Line
Experimental Melanomas
Wnt Signaling Pathway
Melanocytes
Cadherins
Microarray Analysis
Growth
Oligonucleotide Array Sequence Analysis
Cytoskeleton
Nude Mice
Cell Adhesion
Cell Movement
Colon

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

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

In: Genes and Development, Vol. 16, No. 16, 15.08.2002, p. 2058-2072.

Research output: Contribution to journalArticle

Conacci-Sorrell, Maralice E. ; Ben-Yedidia, Tamar ; Shtutman, Michael ; Feinstein, Elena ; Einat, Paz ; Ben-Ze'ev, Avri. / 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. In: Genes and Development. 2002 ; Vol. 16, No. 16. pp. 2058-2072.
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