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

doi:10.1016/j.celrep.2014.02.035

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

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-x_L 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.

Original language	English
Journal	Cell Reports
Volume	7
Issue number	1
Pages (from-to)	208-222
ISSN	2211-1247
DOIs	https://doi.org/10.1016/j.celrep.2014.02.035
Publication status	Published - 4. Oct 2014
Externally published	Yes

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10.1016/j.celrep.2014.02.035Licence: CC BY-NC-ND

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@article{586037059c4f4437acf67f136b988130,

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 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.",

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

year = "2014",

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doi = "10.1016/j.celrep.2014.02.035",

language = "English",

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pages = "208--222",

journal = "Cell Reports",

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publisher = "Cell Press",

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T1 - Death Induced by CD95 or CD95 Ligand Elimination

AU - Hadji, Abbas

AU - Ceppi, Paolo

AU - Murmann, Andrea E.

AU - Brockway, Sonia

AU - Pattanayak, Abhinandan

AU - Bhinder, Bhavneet

AU - Hau, Annika

AU - De Chant, Shirley

AU - Parimi, Vamsi

AU - Kolesza, Piotre

AU - Richards, Jo Anne

AU - Chandel, Navdeep

AU - Djaballah, Hakim

AU - Peter, Marcus E.

PY - 2014/10/4

Y1 - 2014/10/4

N2 - 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.

AB - 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.

U2 - 10.1016/j.celrep.2014.02.035

DO - 10.1016/j.celrep.2014.02.035

M3 - Journal article

C2 - 24656822

AN - SCOPUS:84898024383

SN - 2211-1247

VL - 7

SP - 208

EP - 222

JO - Cell Reports

JF - Cell Reports

IS - 1

ER -

Death Induced by CD95 or CD95 Ligand Elimination

Abstract

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