Identification of membrane-type matrix metalloproteinase-1 as a target of the beta-catenin/Tcf4 complex in human colorectal cancers

Oncogene. 2002 Aug 29;21(38):5861-7. doi: 10.1038/sj.onc.1205755.


Genetic alterations of APC and CTNNB1 (beta-catenin) have been identified in a number of human cancers including tumors arising in the colon and liver. Mutations in these genes lead to abnormal accumulation of beta-catenin and constitutive activation of target genes in the Wnt signaling pathway. To clarify the precise role of accumulated beta-catenin in colorectal carcinogenesis, we searched for genes involved in the beta-catenin/Tcf signaling pathway by cDNA microarray. MT1-MMP (membrane-type matrix metalloproteinase) was among 84 genes that were down-regulated after beta-catenin had been depleted by transduction of wild-type APC in SW480 cells. Expression of MT1-MMP was elevated in 22 of 24 colon carcinomas we examined. Reporter assays and an electromobility-shift assay revealed a DNA fragment between -1169 bp and -1163 bp in the 5' flanking region of this gene to be a target of the beta-catenin/Tcf4 complex. Our results indicate that MT1-MMP is a direct down-stream target in the Wnt signaling pathway, and that one of the ways accumulated beta-catenin contributes to colorectal carcinogenesis is by transactivating this gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Flanking Region
  • Binding Sites
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Cytoskeletal Proteins / metabolism*
  • Humans
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases / genetics*
  • Metalloendopeptidases / metabolism*
  • Promoter Regions, Genetic
  • TCF Transcription Factors
  • Trans-Activators / metabolism*
  • Transcription Factor 7-Like 2 Protein
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured
  • beta Catenin


  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • TCF Transcription Factors
  • TCF7L2 protein, human
  • Trans-Activators
  • Transcription Factor 7-Like 2 Protein
  • Transcription Factors
  • beta Catenin
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases