MUC1 inhibits cell proliferation by a β-catenin-dependent mechanism

Erik P. Lillehoj, Wenju Lu, Timothy Kiser, Simeon E. Goldblum, K. Chul Kim

Research output: Contribution to journalArticle

Abstract

β-Catenin binds to the cytoplasmic region of the type 1 membrane glycoprotein MUC1. In the current study, we utilized HEK293T cells expressing the full-length MUC1 protein, or a CD8/MUC1 fusion protein containing only the MUC1 cytoplasmic tail, to investigate the effects of β-catenin binding to MUC1 on downstream β-catenin-dependent events. Compared with HEK293T cells transfected with empty vector or CD8 alone, expression of the MUC1 cytoplasmic tail inhibited β-catenin binding to E-cadherin, decreased translocation of β-catenin into the nucleus, reduced activation of the LEF-1 transcription factor, and blocked expression of the cyclin D1 and c-Myc proteins. Furthermore, expression of MUC1 was associated with decreased cell proliferation, either in the context of the transfected HEK293T cells, or when comparing wild type (Muc1+/+) vs. knockout (Muc1-/-) mouse primary tracheal epithelial cells. We conclude that MUC1 inhibits cell proliferation through a β-catenin/LEF-1/cyclin D1/c-Myc pathway.

Original languageEnglish (US)
Pages (from-to)1028-1038
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1773
Issue number7
DOIs
StatePublished - Jul 2007

Keywords

  • Cancer
  • Cyclin D1
  • Cytoplasm
  • E-cadherin
  • LEF-1
  • Membrane
  • Nucleus
  • Reepithelialization
  • Transcription
  • c-Myc

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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