CD95 and CD95L promote and protect cancer stem cells

Paolo Ceppi; Abbas Hadji; Frederick J. Kohlhapp; Abhinandan Pattanayak; Annika Hau; Xia Liu; Huiping Liu; Andrea E. Murmann; Marcus E. Peter

doi:10.1038/ncomms6238

CD95 and CD95L promote and protect cancer stem cells

Paolo Ceppi, Abbas Hadji, Frederick J. Kohlhapp, Abhinandan Pattanayak, Annika Hau, Xia Liu, Huiping Liu, Andrea E. Murmann, Marcus E. Peter

Toxicology and Cancer Biology

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

63 Scopus citations

Abstract

CD95 (APO-1/Fas) is a death receptor used by immune cells to kill cancer cells through induction of apoptosis. However, the elimination of CD95 or its ligand, CD95L, from cancer cells results in death induced by CD95R/L elimination (DICE), a type of cell death that resembles a necrotic form of mitotic catastrophe suggesting that CD95 protects cancer cells from cell death. We now report that stimulation of CD95 on cancer cells or reducing miR-200c levels increases the number of cancer stem cells (CSCs), which are more sensitive to induction of DICE than non-CSC, while becoming less sensitive to CD95-mediated apoptosis. In contrast, induction of DICE or overexpression of miR-200c reduces the number of CSCs. We demonstrate that CSCs and non-CSCs have differential sensitivities to CD95-mediated apoptosis and DICE, and that killing of cancer cells can be maximized by concomitant induction of both cell death mechanisms.

Original language	English
Article number	5238
Journal	Nature Communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms6238
State	Published - 2014

Bibliographical note

Publisher Copyright:
© 2014 Macmillan Publishers Limited. All rights reserved.

Funding

This work was funded by a DOD postdoctoral fellowship W81XWH-13-1-0301 (to P.C.), Northern Ohio Golf Charities & Foundation and R00 CA160638 (to H.L.) and a Northwestern Memorial Foundation-Lynn Sage Cancer Research Foundation grant and R01 CA149356 (to M.E.P.).

Funders	Funder number
Northern Ohio Golf Charities & Foundation	R00 CA160638
Northwestern Memorial Foundation-Lynn Sage Cancer Research Foundation	R01 CA149356
U.S. Department of Defense	W81XWH-13-1-0301
National Childhood Cancer Registry – National Cancer Institute	R01CA149356

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

UN SDGs

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

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10.1038/ncomms6238

Cite this

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title = "CD95 and CD95L promote and protect cancer stem cells",

abstract = "CD95 (APO-1/Fas) is a death receptor used by immune cells to kill cancer cells through induction of apoptosis. However, the elimination of CD95 or its ligand, CD95L, from cancer cells results in death induced by CD95R/L elimination (DICE), a type of cell death that resembles a necrotic form of mitotic catastrophe suggesting that CD95 protects cancer cells from cell death. We now report that stimulation of CD95 on cancer cells or reducing miR-200c levels increases the number of cancer stem cells (CSCs), which are more sensitive to induction of DICE than non-CSC, while becoming less sensitive to CD95-mediated apoptosis. In contrast, induction of DICE or overexpression of miR-200c reduces the number of CSCs. We demonstrate that CSCs and non-CSCs have differential sensitivities to CD95-mediated apoptosis and DICE, and that killing of cancer cells can be maximized by concomitant induction of both cell death mechanisms.",

author = "Paolo Ceppi and Abbas Hadji and Kohlhapp, {Frederick J.} and Abhinandan Pattanayak and Annika Hau and Xia Liu and Huiping Liu and Murmann, {Andrea E.} and Peter, {Marcus E.}",

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AU - Ceppi, Paolo

AU - Hadji, Abbas

AU - Kohlhapp, Frederick J.

AU - Pattanayak, Abhinandan

AU - Hau, Annika

AU - Liu, Xia

AU - Liu, Huiping

AU - Murmann, Andrea E.

AU - Peter, Marcus E.

PY - 2014

Y1 - 2014

N2 - CD95 (APO-1/Fas) is a death receptor used by immune cells to kill cancer cells through induction of apoptosis. However, the elimination of CD95 or its ligand, CD95L, from cancer cells results in death induced by CD95R/L elimination (DICE), a type of cell death that resembles a necrotic form of mitotic catastrophe suggesting that CD95 protects cancer cells from cell death. We now report that stimulation of CD95 on cancer cells or reducing miR-200c levels increases the number of cancer stem cells (CSCs), which are more sensitive to induction of DICE than non-CSC, while becoming less sensitive to CD95-mediated apoptosis. In contrast, induction of DICE or overexpression of miR-200c reduces the number of CSCs. We demonstrate that CSCs and non-CSCs have differential sensitivities to CD95-mediated apoptosis and DICE, and that killing of cancer cells can be maximized by concomitant induction of both cell death mechanisms.

AB - CD95 (APO-1/Fas) is a death receptor used by immune cells to kill cancer cells through induction of apoptosis. However, the elimination of CD95 or its ligand, CD95L, from cancer cells results in death induced by CD95R/L elimination (DICE), a type of cell death that resembles a necrotic form of mitotic catastrophe suggesting that CD95 protects cancer cells from cell death. We now report that stimulation of CD95 on cancer cells or reducing miR-200c levels increases the number of cancer stem cells (CSCs), which are more sensitive to induction of DICE than non-CSC, while becoming less sensitive to CD95-mediated apoptosis. In contrast, induction of DICE or overexpression of miR-200c reduces the number of CSCs. We demonstrate that CSCs and non-CSCs have differential sensitivities to CD95-mediated apoptosis and DICE, and that killing of cancer cells can be maximized by concomitant induction of both cell death mechanisms.

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CD95 and CD95L promote and protect cancer stem cells

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

UN SDGs

Access to Document

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