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Cell Rep. 2014 Apr 10;7(1):208-22. doi: 10.1016/j.celrep.2014.02.035. Epub 2014 Mar 20.

Death induced by CD95 or CD95 ligand elimination.

Author information

1
Division of Hematology/Oncology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
2
HTS Core Facility, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
3
Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
4
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
5
Division of Pulmonary and Cell and Molecular Biology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
6
Division of Hematology/Oncology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA. Electronic address: m-peter@northwestern.edu.

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.

PMID:
24656822
PMCID:
PMC4083055
DOI:
10.1016/j.celrep.2014.02.035
[Indexed for MEDLINE]
Free PMC Article

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