The metalloproteinase matrilysin is a target of β-catenin transactivation in intestinal tumors

Howard C. Crawford, Barbara M. Fingleton, Laura A. Rudolph-Owen, Kathleen J. Heppner Goss, Bonnee Rubinfeld, Paul Polakis, Lynn M. Matrisian

Research output: Contribution to journalArticle

596 Citations (Scopus)

Abstract

Matrilysin is a matrix metalloproteinase expressed in the tumor cells of greater than 80% of intestinal adenomas. The majority of these intestinal tumors are associated with the accumulation of β-catenin, a component of the cadherin adhesion complex and, through its association with the T Cell Factor (Tcf) DNA binding proteins, a regulator in the Wnt signal transduction pathway. In murine intestinal tumors, matrilysin transcripts show striking overlap with the accumulation of β-catenin protein. The matrilysin promoter is upregulated as much as 12-fold by β-catenin in colon tumor cell lines in a manner inversely proportional to the endogenous levels of β-catenin/Tcf complex and is dependent upon a single optimal Tcf-4 recognition site. Coexpression of the E-cadherin cytoplasmic domain blocked this induction and reduced basal promoter activity in every colon cancer cell line tested. Inactivation of the Tcf binding site increased promoter activity and overexpression of the Tcf factor, LEF-1, significantly downregulated matrilysin promoter activity, suggesting that β-catenin transactivates the matrilysin promoter by virtue of its ability to abrogate Tcf-mediated repression. Because genetic ablation of matrilysin decreases tumor formation in multiple intestinal neoplasia (Min) mice, we propose that regulation of matrilysin production by β-catenin accumulation is a contributing factor to intestinal tumorigenesis.

Original languageEnglish (US)
Pages (from-to)2883-2891
Number of pages9
JournalOncogene
Volume18
Issue number18
DOIs
StatePublished - May 6 1999
Externally publishedYes

Fingerprint

Matrix Metalloproteinase 7
Catenins
Metalloproteases
TCF Transcription Factors
Transcriptional Activation
Neoplasms
Cadherins
Transcription Factor 7-Like 2 Protein
DNA-Binding Proteins
Tumor Cell Line
Matrix Metalloproteinases
Adenoma
Colonic Neoplasms
Signal Transduction
Colon
Carcinogenesis
Down-Regulation
Binding Sites
Cell Line

Keywords

  • β-catenin
  • APC
  • Matrilysin
  • Tcf
  • Tumorigenesis

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

Crawford, H. C., Fingleton, B. M., Rudolph-Owen, L. A., Heppner Goss, K. J., Rubinfeld, B., Polakis, P., & Matrisian, L. M. (1999). The metalloproteinase matrilysin is a target of β-catenin transactivation in intestinal tumors. Oncogene, 18(18), 2883-2891. https://doi.org/10.1038/sj.onc.1202627

The metalloproteinase matrilysin is a target of β-catenin transactivation in intestinal tumors. / Crawford, Howard C.; Fingleton, Barbara M.; Rudolph-Owen, Laura A.; Heppner Goss, Kathleen J.; Rubinfeld, Bonnee; Polakis, Paul; Matrisian, Lynn M.

In: Oncogene, Vol. 18, No. 18, 06.05.1999, p. 2883-2891.

Research output: Contribution to journalArticle

Crawford, HC, Fingleton, BM, Rudolph-Owen, LA, Heppner Goss, KJ, Rubinfeld, B, Polakis, P & Matrisian, LM 1999, 'The metalloproteinase matrilysin is a target of β-catenin transactivation in intestinal tumors', Oncogene, vol. 18, no. 18, pp. 2883-2891. https://doi.org/10.1038/sj.onc.1202627
Crawford HC, Fingleton BM, Rudolph-Owen LA, Heppner Goss KJ, Rubinfeld B, Polakis P et al. The metalloproteinase matrilysin is a target of β-catenin transactivation in intestinal tumors. Oncogene. 1999 May 6;18(18):2883-2891. https://doi.org/10.1038/sj.onc.1202627
Crawford, Howard C. ; Fingleton, Barbara M. ; Rudolph-Owen, Laura A. ; Heppner Goss, Kathleen J. ; Rubinfeld, Bonnee ; Polakis, Paul ; Matrisian, Lynn M. / The metalloproteinase matrilysin is a target of β-catenin transactivation in intestinal tumors. In: Oncogene. 1999 ; Vol. 18, No. 18. pp. 2883-2891.
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