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 › Article › peer-review

44 Scopus citations

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 (US)
Pages (from-to)	208-222
Number of pages	15
Journal	Cell reports
Volume	7
Issue number	1
DOIs	https://doi.org/10.1016/j.celrep.2014.02.035
State	Published - Oct 4 2014

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.celrep.2014.02.035

Cite this

@article{4894d67bc7e1428fa98c8ea1877ac2c8,

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.}",

note = "Funding Information: We are grateful to Drs. E. Lengyel and A. Mitra for providing primary omental fibroblasts. We would like to thank Drs. B. Vogelstein for providing the HCT116 TP53 −/− and HCT116 DICER −/− cells, T. Li for performing the tissue stainings for CD95, and Sam Bettis for performing the small molecule screen. We would also like to thank Drs. J. Lahti, J. Rossi, and Zhen-Gang Liu for providing the NB7 cells, the Tet-inducible vector, and the MLKL knockdown cells, respectively. We thank Dr. J. Licht for help in performing comet assays. The HTS Core Facility is supported by Mr. William H. Goodwin and Mrs. Alice Goodwin, the Commonwealth Foundation for Cancer Research, the ETC of MSKCC, the Lillian S. Wells Foundation, and by a NIH/NCI Cancer Center Support Grant 5 P30 CA008748-44. S.B. is supported in part by NIH/NCI training grant T32CA09560. This work was funded by the NCI (RO1 CA112240 to M.E.P.). ",

year = "2014",

month = oct,

day = "4",

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

language = "English (US)",

volume = "7",

pages = "208--222",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "1",

}

Death Induced by CD95 or CD95 Ligand Elimination. / Hadji, Abbas; Ceppi, Paolo; Murmann, Andrea E.; Brockway, Sonia; Pattanayak, Abhinandan; Bhinder, Bhavneet; Hau, Annika; De Chant, Shirley; Parimi, Vamsi; Kolesza, Piotre; Richards, Jo Anne; Chandel, Navdeep; Djaballah, Hakim; Peter, Marcus E.

In: Cell reports, Vol. 7, No. 1, 04.10.2014, p. 208-222.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

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.

N1 - Funding Information: We are grateful to Drs. E. Lengyel and A. Mitra for providing primary omental fibroblasts. We would like to thank Drs. B. Vogelstein for providing the HCT116 TP53 −/− and HCT116 DICER −/− cells, T. Li for performing the tissue stainings for CD95, and Sam Bettis for performing the small molecule screen. We would also like to thank Drs. J. Lahti, J. Rossi, and Zhen-Gang Liu for providing the NB7 cells, the Tet-inducible vector, and the MLKL knockdown cells, respectively. We thank Dr. J. Licht for help in performing comet assays. The HTS Core Facility is supported by Mr. William H. Goodwin and Mrs. Alice Goodwin, the Commonwealth Foundation for Cancer Research, the ETC of MSKCC, the Lillian S. Wells Foundation, and by a NIH/NCI Cancer Center Support Grant 5 P30 CA008748-44. S.B. is supported in part by NIH/NCI training grant T32CA09560. This work was funded by the NCI (RO1 CA112240 to M.E.P.).

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.

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U2 - 10.1016/j.celrep.2014.02.035

DO - 10.1016/j.celrep.2014.02.035

M3 - Article

C2 - 24656822

AN - SCOPUS:84898024383

VL - 7

SP - 208

EP - 222

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 1

ER -

Death Induced by CD95 or CD95 Ligand Elimination

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