β-catenin/Wnt signaling regulates expression of the membrane type 3 matrix metalloproteinase in gastric cancer

Andrew M. Lowy, Wilson M. Clements, John W Bishop, Ling Kong, Tera Bonney, Karena Sisco, Bruce Aronow, Cecilia Fenoglio-Preiser, Joanna Groden

Research output: Contribution to journalArticle

83 Scopus citations

Abstract

Activation of Wnt signaling through β-catenin dysregulation occurs in numerous human tumors, including gastric cancer. The specific consequences of Wnt signaling in gastric cancer, however, are not well characterized. This study shows that the introduction of mutant β-catenin into gastric cancer cell lines by adenoviral infection enhances invasiveness and proliferation and up-regulates the expression of the gene encoding the matrix metalloproteinase (MMP) family member membrane type 3 MMP (MT3-MMP). Up-regulation of MT3-MMP is critical to the invasive phenotype as shown by small interfering RNA (siRNA) studies. Immunohistochemical staining also showed that MT3-MMP was highly expressed in gastric cancers with activating β-catenin mutations. These observations suggest that Wnt activation may contribute to gastric cancer progression by increasing the invasiveness of neoplastic cells in the stomach via up-regulation of MT3-MMP expression.

Original languageEnglish (US)
Pages (from-to)4734-4741
Number of pages8
JournalCancer Research
Volume66
Issue number9
DOIs
StatePublished - May 1 2006
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Lowy, A. M., Clements, W. M., Bishop, J. W., Kong, L., Bonney, T., Sisco, K., Aronow, B., Fenoglio-Preiser, C., & Groden, J. (2006). β-catenin/Wnt signaling regulates expression of the membrane type 3 matrix metalloproteinase in gastric cancer. Cancer Research, 66(9), 4734-4741. https://doi.org/10.1158/0008-5472.CAN-05-4268