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CD74-dependent deregulation of the tumor suppressor scribble in human epithelial and breast cancer cells

Gergana Metodieva1, Naiara Correa Nogueira-de-Souza, Christina Greenwood

  • 1Proteomics Unit, Department of Biological Sciences, University of Essex, Colchester, Essex, United Kingdom.

Neoplasia (New York, N.Y.)
|June 5, 2013
PubMed

Insights

Overexpression of CD74 in breast cancer disrupts the tumor suppressor Scribble, increasing cancer cell motility and invasiveness. This finding offers new insights into metastatic breast tumor progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • CD74 (gamma subunit of MHC class II) is overexpressed in metastatic breast tumors.
  • The biological significance and underlying mechanisms of CD74 overexpression are not fully understood.

Purpose of the Study:

  • To investigate the interaction between CD74 and Scribble in cancer cells.
  • To elucidate the functional consequences of CD74 overexpression on Scribble's activity and cellular behavior.

Main Methods:

  • Utilized human cancer and noncancerous epithelial cells with CD74 overexpression.
  • Employed tetracycline-inducible promoter systems for controlled CD74 expression.
  • Applied quantitative high-resolution mass spectrometry to analyze protein phosphorylation.

Main Results:

  • CD74 interacts with and interferes with the function of Scribble, a tumor suppressor.
  • CD74 overexpression alters Scribble's C-terminal phosphorylation patterns.
  • Scribble translocates from cell-to-cell contacts to the cytoplasm, enhancing cancer cell motility and invasiveness.

Conclusions:

  • CD74 overexpression promotes cancer cell invasiveness by disrupting Scribble.
  • This mechanism represents a potential therapeutic target for metastatic breast cancer.

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