miR-200c regulates induction of apoptosis through CD95 by targeting FAP-1

Mol Cell. 2010 Jun 25;38(6):908-15. doi: 10.1016/j.molcel.2010.05.018.


Tumor progression shares many characteristics with the process of epithelial-to-mesenchymal transition (EMT). Cells that have undergone an EMT are known to have an increased resistance to apoptosis. CD95/Fas is an apoptosis-inducing receptor expressed on many tissues and tumor cells. During tumor progression CD95 is frequently downregulated, and tumor cells lose apoptosis sensitivity. miR-200 microRNAs repress both the EMT-inducing ZEB1 and ZEB2 transcription factors. We now demonstrate that miR-200c sensitizes cells to apoptosis mediated by CD95. We have identified the apoptosis inhibitor FAP-1 as a target for miR-200c. FAP-1 was demonstrated to be responsible for the reduced sensitivity to CD95-mediated apoptosis in cells with inhibited miR-200. The identification of FAP-1 as an miR-200c target provides a molecular mechanism to explain both the downregulation of CD95 expression and the reduction in sensitivity of cells to CD95-mediated apoptosis that is observed in the context of reduced miR-200 expression during tumor progression.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Apoptosis*
  • Cell Line, Tumor
  • Humans
  • MicroRNAs / metabolism*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 13 / metabolism*
  • fas Receptor / metabolism*


  • FAS protein, human
  • MIRN200 microRNA, human
  • MicroRNAs
  • fas Receptor
  • PTPN13 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 13