title: CD95 and CD95L promote and protect cancer stem cells.
abstract: CD95 (APO-1/Fas) is a death receptor used by immune cells to kill cancer cells through induction of apoptosis. However, the elimination of CD95 or its ligand, CD95L, from cancer cells results in death induced by CD95R/L elimination (DICE), a type of cell death that resembles a necrotic form of mitotic catastrophe suggesting that CD95 protects cancer cells from cell death. We now report that stimulation of CD95 on cancer cells or reducing miR-200c levels increases the number of cancer stem cells (CSCs), which are more sensitive to induction of DICE than non-CSC, while becoming less sensitive to CD95-mediated apoptosis. In contrast, induction of DICE or overexpression of miR-200c reduces the number of CSCs. We demonstrate that CSCs and non-CSCs have differential sensitivities to CD95-mediated apoptosis and DICE, and that killing of cancer cells can be maximized by concomitant induction of both cell death mechanisms.
authors.affiliation: Division Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ceppi
authors.affiliation: Division Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Abbas
authors.initials: A
authors.lastname: Hadji
authors.affiliation: Division Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Kohlhapp
authors.affiliation: Division Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Abhinandan
authors.initials: A
authors.lastname: Pattanayak
authors.affiliation: Division Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Annika
authors.initials: A
authors.lastname: Hau
authors.affiliation: Department of Pathology and Case Comprehensive Cancer Center, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pathology and Case Comprehensive Cancer Center, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: Huiping
authors.initials: H
authors.lastname: Liu
authors.affiliation: Division Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Murmann
authors.affiliation: Division Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Peter
mesh_terms: D000818:Animals; D017209:Apoptosis; D053222:Fas Ligand Protein / Q000378:metabolism*; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism*
chemical_list: C491901:FAS protein, human; D053222:Fas Ligand Protein; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D019014:fas Receptor