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

Research output: Contribution to journalArticlepeer-review

62 Scopus citations


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 languageEnglish
Article number5238
JournalNature Communications
StatePublished - 2014

Bibliographical 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.).

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

ASJC Scopus subject areas

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


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