A minimal fragment of MUC1 mediates growth of cancer cells

PLoS One. 2008 Apr 30;3(4):e2054. doi: 10.1371/journal.pone.0002054.

Abstract

The MUC1 protein is aberrantly expressed on many solid tumor cancers. In contrast to its apical clustering on healthy epithelial cells, it is uniformly distributed over cancer cells. However, a mechanistic link between aberrant expression and cancer has remained elusive. Herein, we report that a membrane-bound MUC1 cleavage product, that we call MUC1*, is the predominant form of the protein on cultured cancer cells and on cancerous tissues. Further, we demonstrate that transfection of a minimal fragment of MUC1, MUC1*(1110), containing a mere forty-five (45) amino acids of the extracellular domain, is sufficient to confer the oncogenic activities that were previously attributed to the full-length protein. By comparison of molecular weight and function, it appears that MUC1* and MUC1*(1110) are approximately equivalent. Evidence is presented that strongly supports a mechanism whereby dimerization of the extracellular domain of MUC1* activates the MAP kinase signaling cascade and stimulates cell growth. These findings suggest methods to manipulate this growth mechanism for therapeutic interventions in cancer treatments.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies
  • Cell Membrane / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • Humans
  • Ligands
  • Molecular Sequence Data
  • Mucin-1 / chemistry
  • Mucin-1 / metabolism*
  • Mutant Proteins / metabolism
  • Neoplasms / pathology*
  • Peptide Fragments / metabolism*
  • Protein Structure, Tertiary
  • Rats
  • Receptors, Growth Factor / metabolism

Substances

  • Antibodies
  • Ligands
  • Mucin-1
  • Mutant Proteins
  • Peptide Fragments
  • Receptors, Growth Factor