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CD95 promotes tumour growth

机译：CD95促进肿瘤生长

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摘要

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 frequently 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.
机译：CD95（也称为Fas和APO-1）是一种原型死亡受体，主要通过诱导细胞凋亡来调节免疫系统中的组织稳态。在癌症进展过程中，CD95经常下调或使细胞具有凋亡抗性，从而增加了CD95缺失是逃避肿瘤机制的一部分的可能性。然而，在人类癌症中很少见到CD95完全丧失，许多癌细胞在体外表达大量CD95，并对CD95介导的细胞凋亡高度敏感。此外，癌症患者经常具有升高水平的CD95，CD95L的生理配体。这些数据增加了CD95可能通过其非凋亡活性实际上促进肿瘤生长的可能性。在这里，我们显示了癌细胞，一般而言，无论其对CD95细胞凋亡的敏感性如何，都依赖于由癌症产生的CD95L刺激的CD95的组成型活性，以实现最佳生长。一致地，在卵巢癌和肝癌的小鼠模型中CD95的缺失减少了癌症的发病率以及肿瘤的大小。 CD95的致癌活性是由涉及JNK和Jun的途径介导的。这些结果表明，CD95在肿瘤发生过程中具有促进生长的作用，并表明在癌症治疗期间应考虑抑制其活性而不是增强其活性。

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  • 来源
    《Nature》 |2010年第7297期|p.492-496|共5页
  • 作者

    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;

  • 作者单位

    The Ben May Department tor Cancer Research, The University of Chicago, 924 E 57th Street, Chicago, Illinois 60637, USA Northwestern University Feinberg School of Medicine, 303 East Superior Street, Chicago, Illinois 60611, USA;

    The Ben May Department tor Cancer Research, The University of Chicago, 924 E 57th Street, Chicago, Illinois 60637, USA;

    Department of Pathology, The University of Chicago, 5841 South Maryland Avenue, Chicago, Illinois 60637, USA;

    The Ben May Department tor Cancer Research, The University of Chicago, 924 E 57th Street, Chicago, Illinois 60637, USA Northwestern University Feinberg School of Medicine, 303 East Superior Street, Chicago, Illinois 60611, USA;

    Department of Obstetrics and Gynecology/Section of Gynecologic Oncology, The University of Chicago, 5841 South Maryland Avenue, Chicago, Illinois 60637, USA Osaka University Graduate School of Medicine, Department of Obstetrics & Gynecology, 2-2, Yamadaoka, Suita, Osaka 565-0879, Japan;

    The Ben May Department tor Cancer Research, The University of Chicago, 924 E 57th Street, Chicago, Illinois 60637, USA Cambridge Research Institute/Cancer Research UK, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK;

    Department of Pathology, The University of Chicago, 5841 South Maryland Avenue, Chicago, Illinois 60637, USA;

    Department of Pathology, The University of Chicago, 5841 South Maryland Avenue, Chicago, Illinois 60637, USA;

    Department of Obstetrics and Gynecology/Section of Gynecologic Oncology, The University of Chicago, 5841 South Maryland Avenue, Chicago, Illinois 60637, USA;

    Department of Obstetrics and Gynecology/Section of Gynecologic Oncology, The University of Chicago, 5841 South Maryland Avenue, Chicago, Illinois 60637, USA;

    The Ben May Department tor Cancer Research, The University of Chicago, 924 E 57th Street, Chicago, Illinois 60637, USA Northwestern University Feinberg School of Medicine, 303 East Superior Street, Chicago, Illinois 60611, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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