CD95 promotes tumour growth.
CD95 promotes tumour growth.
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CD95(又称Fas和APO-1)是一种典型的死亡受体，主要通过诱导细胞凋亡来调节组织的动态平衡。在癌症进展过程中，CD95经常被下调或使细胞具有抗凋亡能力，这增加了CD95丢失是肿瘤逃逸机制的一部分的可能性。然而，CD95的完全缺失在人类肿瘤中很少见，许多肿瘤细胞表达大量的CD95，并且对CD95介导的体外细胞凋亡高度敏感。此外，癌症患者CD95、CD95L的生理配体水平经常升高。这些数据提出了一个耐人寻味的可能性，即CD95实际上可以通过其非凋亡活性促进肿瘤的生长。在这里，我们表明，一般说来，癌细胞，无论其对CD95凋亡的敏感性，都依赖于CD95的构成活性，由癌症产生的CD95L刺激，以实现最佳生长。在卵巢癌和肝癌的小鼠模型中，CD95的缺失一贯地降低了癌症的发病率和肿瘤的大小。CD95的致瘤活性是通过JNK和c-jun途径介导的。这些结果表明CD95在肿瘤发生过程中起着促进生长的作用，并提示在癌症治疗中应考虑抑制其活性而不是增强其激活的努力。
CD95 (also called Fas and APO-1) is a prototypical death receptor that regulates tissue homeostasis mainly in the immune system through 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 intriguing possibility that CD95 could actually promote the growth of tumours through its nonapoptotic 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 c-Jun. These results demonstrate that CD95 plays a growth promoting role during tumorigenesis and suggest that efforts to inhibit its activity rather than to enhance its activation should be considered during cancer therapy.
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影响因子：
82.9
作者：
Dinulescu, DM;Ince, TA;Jacks, T
通讯作者：
Jacks, T
影响因子：
23.9
作者：
Corsini, Nina S.;Sancho-Martinez, Ignacio;Martin-Villalba, Ana
通讯作者：
Martin-Villalba, Ana
影响因子：
1.9
作者：
Greene, AK;Puder, M
通讯作者：
Puder, M
口服避孕药或促性腺激素释放激素激动剂对基因工程小鼠卵巢癌发生的影响。
DOI：
10.1158/1940-6207.capr-08-0236
发表时间：
2009-09
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Romero IL;Gordon IO;Jagadeeswaran S;Mui KL;Lee WS;Dinulescu DM;Krausz TN;Kim HH;Gilliam ML;Lengyel E
通讯作者：
Lengyel E
影响因子：
32.4
作者：
Strasser, Andreas;Jost, Philipp J.;Nagata, Shigekazu
通讯作者：
Nagata, Shigekazu