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^*

^*Corresponding author for this work

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

36 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 (US)
Article number	5238
Journal	Nature communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms6238
State	Published - 2014

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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@article{56de60cc73d04e8187db068863a14737,

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.}",

note = "Funding Information: 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.).",

year = "2014",

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T1 - CD95 and CD95L promote and protect cancer stem cells

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.

N1 - Funding Information: 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.).

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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