Death Induced by CD95 or CD95 Ligand Elimination

Abbas Hadji, Paolo Ceppi, Andrea E. Murmann, Sonia Brockway, Abhinandan Pattanayak, Bhavneet Bhinder, Annika Hau, Shirley De Chant, Vamsi Parimi, Piotre Kolesza, Jo Anne Richards, Navdeep Chandel, Hakim Djaballah, Marcus E. Peter*

*Kontaktforfatter for dette arbejde

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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 incell 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.

TidsskriftCell Reports
Udgave nummer1
Sider (fra-til)208-222
Antal sider15
StatusUdgivet - 4. okt. 2014

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