CD95 promotes tumour growth

Lina Chen, Sun Mi Park, Alexei V. Tumanov, Annika Hau, Kenjiro Sawada, Christine Feig, Jerrold R. Turner, Yang Xin Fu, Iris L. Romero, Ernst Lengyel, Marcus E. Peter

Research output: Contribution to journalArticle

250 Citations (Scopus)

Abstract

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 apoptosis. During cancer progression CD95 is frequntly downregulated or cells are rendered apoptosis resistant, 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 cancers 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, CD95L. These data raise the possibility that CD95 could actually promote the growth of tumours through its non-apoptotic activities. 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.

Original languageEnglish (US)
Pages (from-to)492-496
Number of pages5
JournalNature
Volume465
Issue number7297
DOIs
StatePublished - May 27 2010

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Growth
Neoplasms
Fas Ligand Protein
Apoptosis
Liver Neoplasms
Death Domain Receptors
MAP Kinase Signaling System
Ovarian Neoplasms
Immune System
Carcinogenesis
Homeostasis
Down-Regulation
Incidence

ASJC Scopus subject areas

  • General

Cite this

Chen, L., Park, S. M., Tumanov, A. V., Hau, A., Sawada, K., Feig, C., ... Peter, M. E. (2010). CD95 promotes tumour growth. Nature, 465(7297), 492-496. https://doi.org/10.1038/nature09075

CD95 promotes tumour growth. / Chen, Lina; Park, Sun Mi; Tumanov, Alexei V.; Hau, Annika; Sawada, Kenjiro; Feig, Christine; Turner, Jerrold R.; Fu, Yang Xin; Romero, Iris L.; Lengyel, Ernst; Peter, Marcus E.

In: Nature, Vol. 465, No. 7297, 27.05.2010, p. 492-496.

Research output: Contribution to journalArticle

Chen, L, Park, SM, Tumanov, AV, Hau, A, Sawada, K, Feig, C, Turner, JR, Fu, YX, Romero, IL, Lengyel, E & Peter, ME 2010, 'CD95 promotes tumour growth', Nature, vol. 465, no. 7297, pp. 492-496. https://doi.org/10.1038/nature09075
Chen L, Park SM, Tumanov AV, Hau A, Sawada K, Feig C et al. CD95 promotes tumour growth. Nature. 2010 May 27;465(7297):492-496. https://doi.org/10.1038/nature09075
Chen, Lina ; Park, Sun Mi ; Tumanov, Alexei V. ; Hau, Annika ; Sawada, Kenjiro ; Feig, Christine ; Turner, Jerrold R. ; Fu, Yang Xin ; Romero, Iris L. ; Lengyel, Ernst ; Peter, Marcus E. / CD95 promotes tumour growth. In: Nature. 2010 ; Vol. 465, No. 7297. pp. 492-496.
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