Loss of Scribble causes cell competition in mammalian cells

J Cell Sci. 2012 Jan 1;125(Pt 1):59-66. doi: 10.1242/jcs.085803. Epub 2012 Jan 16.


In Drosophila, normal and transformed cells compete with each other for survival in a process called cell competition. However, it is not known whether comparable phenomena also occur in mammals. Scribble is a tumor suppressor protein in Drosophila and mammals. In this study we examine the interface between normal and Scribble-knockdown epithelial cells using Madin-Darby Canine Kidney (MDCK) cells expressing Scribble short hairpin RNA (shRNA) in a tetracycline-inducible manner. We observe that Scribble-knockdown cells undergo apoptosis and are apically extruded from the epithelium when surrounded by normal cells. Apoptosis does not occur when Scribble-knockdown cells are cultured alone, suggesting that the presence of surrounding normal cells induces the cell death. We also show that death of Scribble-knockdown cells occurs independently of apical extrusion. Finally, we demonstrate that apoptosis of Scribble-knockdown cells depends on activation of p38 mitogen-activated protein kinase (MAPK). This is the first demonstration that an oncogenic transformation within an epithelium induces cell competition in a mammalian cell culture system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Line
  • Cell Polarity
  • Cell Shape
  • Dogs
  • Drosophila Proteins*
  • Enzyme Activation
  • Epithelial Cells / cytology*
  • Epithelial Cells / metabolism*
  • Gene Knockdown Techniques
  • Membrane Proteins / deficiency*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Drosophila Proteins
  • Membrane Proteins
  • Scrib protein, Drosophila
  • p38 Mitogen-Activated Protein Kinases