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

Robert Schickel*, Sun Mi Park, Andrea E. Murmann, Marcus E. Peter

*Corresponding author for this work

Research output: Contribution to journalArticle

134 Scopus citations

Abstract

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. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Original languageEnglish (US)
Pages (from-to)908-915
Number of pages8
JournalMolecular cell
Volume38
Issue number6
DOIs
StatePublished - Jun 25 2010

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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