title: Death induced by CD95 or CD95 ligand elimination.
abstract: CD95 (Fas/APO-1), when bound by its cognate ligand CD95L, induces cells to die by apoptosis. We now show that elimination of CD95 or CD95L results in a form of cell death that is independent of caspase-8, RIPK1/MLKL, and p53, is not inhibited by Bcl-xL expression, and preferentially affects cancer cells. All tumors that formed in mouse models of low-grade serous ovarian cancer or chemically induced liver cancer with tissue-specific deletion of CD95 still expressed CD95, suggesting that cancer cannot form in the absence of CD95. Death induced by CD95R/L elimination (DICE) is characterized by an increase in cell size, production of mitochondrial ROS, and DNA damage. It resembles a necrotic form of mitotic catastrophe. No single drug was found to completely block this form of cell death, and it could also not be blocked by the knockdown of a single gene, making it a promising way to kill cancer cells.
authors.affiliation: Division of Hematology/Oncology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Abbas
authors.initials: A
authors.lastname: Hadji
authors.affiliation: Division of Hematology/Oncology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ceppi
authors.affiliation: Division of Hematology/Oncology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Murmann
authors.affiliation: Division of Hematology/Oncology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Sonia
authors.initials: S
authors.lastname: Brockway
authors.affiliation: Division of Hematology/Oncology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Abhinandan
authors.initials: A
authors.lastname: Pattanayak
authors.affiliation: HTS Core Facility, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Bhavneet
authors.initials: B
authors.lastname: Bhinder
authors.affiliation: Division of Hematology/Oncology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Annika
authors.initials: A
authors.lastname: Hau
authors.affiliation: Division of Hematology/Oncology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Shirley
authors.initials: S
authors.lastname: De Chant
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Vamsi
authors.initials: V
authors.lastname: Parimi
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Piotre
authors.initials: P
authors.lastname: Kolesza
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Joanne
authors.initials: J
authors.lastname: Richards
authors.affiliation: Division of Pulmonary and Cell and Molecular Biology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Navdeep
authors.initials: N
authors.lastname: Chandel
authors.affiliation: HTS Core Facility, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Hakim
authors.initials: H
authors.lastname: Djaballah
authors.affiliation: Division of Hematology/Oncology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA. Electronic address: m-peter@northwestern.edu.
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Peter
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D053222:Fas Ligand Protein / Q000172:deficiency* / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D045325:HCT116 Cells; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D019014:fas Receptor / Q000172:deficiency* / Q000378:metabolism
chemical_list: D053222:Fas Ligand Protein; D019014:fas Receptor