Tumor promoting effects of CD95 signaling in chemoresistant cells.
Tumor promoting effects of CD95 signaling in chemoresistant cells.
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DOI：
10.1186/1476-4598-9-161
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发表时间：
2010-06-23
期刊：
影响因子：
37.3
通讯作者：
Almendro V
中科院分区：
文献类型：
--
作者：
Ametller E;García-Recio S;Costamagna D;Mayordomo C;Fernández-Nogueira P;Carbó N;Pastor-Arroyo EM;Gascón P;Almendro V
CD95是一种死亡受体，不仅控制凋亡途径，而且激活促进肿瘤生长的机制。在获得对奥沙利铂的化学抗性期间，结肠癌细胞中的CD95表达逐渐丧失，并且该受体诱导细胞死亡的能力降低。本研究的目的是表征奥沙利铂耐药结肠癌细胞中由CD95信号转导控制的一些关键细胞反应。我们发现，CD95触发导致耐药细胞转移能力增加。此外，奥沙利铂治疗本身通过CD95活化刺激细胞迁移并降低细胞粘附，因为siRNA抑制CD95表达阻断了奥沙利铂的促迁移作用。这些促迁移作用与上皮细胞向间充质细胞转化（EMT）现象有关，如通过在体外和体内上调一些转录因子和间充质细胞标志物所证明的。我们得出结论，奥沙利铂治疗对奥沙利铂诱导的细胞凋亡具有获得性耐药性的细胞，通过激活CD95信号传导和诱导EMT产生肿瘤促进作用，所有这些事件共同促成了转移表型。
CD95 is a death receptor controlling not only apoptotic pathways but also activating mechanisms promoting tumor growth. During the acquisition of chemoresistance to oxaliplatin there is a progressive loss of CD95 expression in colon cancer cells and a decreased ability of this receptor to induce cell death. The aim of this study was to characterize some key cellular responses controlled by CD95 signaling in oxaliplatin-resistant colon cancer cells. We show that CD95 triggering results in an increased metastatic ability in resistant cells. Moreover, oxaliplatin treatment itself stimulates cell migration and decreases cell adhesion through CD95 activation, since CD95 expression inhibition by siRNA blocks the promigratory effects of oxaliplatin. These promigratory effects are related to the epithelia-to-mesenchymal transition (EMT) phenomenon, as evidenced by the up-regulation of some transcription factors and mesenchymal markers both in vitro and in vivo. We conclude that oxaliplatin treatment in cells that have acquired resistance to oxaliplatin-induced apoptosis results in tumor-promoting effects through the activation of CD95 signaling and by inducing EMT, all these events jointly contributing to a metastatic phenotype.
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影响因子：
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作者：
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影响因子：
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