title: miR-200c regulates induction of apoptosis through CD95 by targeting FAP-1.
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.
authors.affiliation: The Ben May Department for Cancer Research, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Schickel
authors.forename: Sun-Mi
authors.initials: SM
authors.lastname: Park
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Murmann
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Peter
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13 / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism*
chemical_list: C491901:FAS protein, human; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D019014:fas Receptor; C516742:PTPN13 protein, human; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13