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CD95 promotes tumour growth

A Corrigendum to this article was published on 14 November 2012

A Corrigendum to this article was published on 22 June 2011

A Corrigendum to this article was published on 09 March 2011

This article has been updated


CD95 (also called Fas and APO-1) is a prototypical death receptor that regulates tissue homeostasis mainly in the immune system through the induction of apoptosis1,2,3. During cancer progression CD95 is frequently downregulated or cells are rendered apoptosis resistant4,5, raising the possibility that loss of CD95 is part of a mechanism for tumour evasion. However, complete loss of CD95 is rarely seen in human cancers4 and many cancer cells express large quantities of CD95 and are highly sensitive to CD95-mediated apoptosis in vitro. Furthermore, cancer patients frequently have elevated levels of the physiological ligand for CD95, CD95L6. These data raise the possibility that CD95 could actually promote the growth of tumours through its non-apoptotic activities7. Here we show that cancer cells in general, regardless of their CD95 apoptosis sensitivity, depend on constitutive activity of CD95, stimulated by cancer-produced CD95L, for optimal growth. Consistently, loss of CD95 in mouse models of ovarian cancer and liver cancer reduces cancer incidence as well as the size of the tumours. The tumorigenic activity of CD95 is mediated by a pathway involving JNK and Jun. These results demonstrate that CD95 has a growth-promoting role during tumorigenesis and indicate that efforts to inhibit its activity rather than to enhance it should be considered during cancer therapy.

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Figure 1: Reducing CD95 or CD95L expression inhibits proliferation of cancer cells.
Figure 2: Loss of CD95 expression inhibits ovarian cancer in vivo.
Figure 3: Deletion of CD95 leads to a reduction in tumour formation in a spontaneous model of endometrioid ovarian cancer.
Figure 4: Deletion of CD95 in the liver leads to a decrease in tumour formation caused by the reduced ability of hepatocytes to proliferate and to activate JNK.

Change history

  • 14 November 2012

    Nature 465, 492–496 (2010); doi:10.1038/nature09075 In Fig. 1f of the original Letter, an incorrect actin blot was published: see the corrected panel in Fig. 1 of this Corrigendum. Also, in the original Supplementary Fig. 12c, some of the western blot data were either misinterpreted or raw data could not be located.


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We are grateful to A. Chervonsky and D. Dinulescu for providing the CD95loxP/loxP mice and the KrasG12D/+Ptenfl/fl mice, respectively, and to S. Ahmed for help with one experiment. We are grateful to T. Li for performing the immunohistochemistry and to Y.-J. Hua for analysing the gene array data. This work was funded by grants CA112240 from the NCI and CCFA 1661 from the Crohn's and Colitis Foundation of America (to M.E.P.) and the Burroughs Wellcome Fund, the Ovarian Cancer Research Fund and RO1 CA11182 from the NCI (to E.L.).

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Authors and Affiliations



L.C. and S.M.P performed the experiments; A.V.T. performed the partial hepatectomy; A.H., K.S., C.F. and I.L.R. performed some experiments; J.R.T. performed pathology analyses; Y.-X.F. and E.L. supervised some experiments; M.E.P designed experiments and supervised the project.

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Correspondence to Marcus E. Peter.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Figures 1-13 with legends, Supplementary Results, Supplementary Materials and Methods and additional references. Supplementary Fig. 8 and Supplementary Methods were replaced on 9 March 2011. (PDF 3852 kb)

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Chen, L., Park, SM., Tumanov, A. et al. CD95 promotes tumour growth. Nature 465, 492–496 (2010).

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