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首页> 外文期刊>Cell death & disease. >WRAP53 promotes cancer cell survival and is a potential target for cancer therapy
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WRAP53 promotes cancer cell survival and is a potential target for cancer therapy

机译：WRAP53促进癌细胞存活，是癌症治疗的潜在靶标

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We previously identified WRAP53 as an antisense transcript that regulates the p53 tumor suppressor. The WRAP53 gene also encodes a protein essential for Cajal body formation and involved in cellular trafficking of the survival of motor neuron complex, the telomerase enzyme and small Cajal body-specific RNAs to Cajal bodies. Here, we show that the WRAP53 protein is overexpressed in a variety of cancer cell lines of different origin and that WRAP53 overexpression promotes cellular transformation. Knockdown of the WRAP53 protein triggers massive apoptosis through the mitochondrial pathway, as demonstrated by Bax/Bak activation, loss of mitochondrial membrane potential and cytochrome c release. The apoptosis induced by WRAP53 knockdown could moreover be blocked by Bcl-2 overexpression. Interestingly, human tumor cells are more sensitive to WRAP53 depletion as compared with normal human cells indicating that cancer cells in particular depends on WRAP53 expression for their survival. In agreement with this, we found that high levels of WRAP53 correlate with poor prognosis of head and neck cancer. Together these observations propose a role of WRAP53 in carcinogenesis and identify WRAP53 as a novel molecular target for a large fraction of malignancies.. ? 2011 Macmillan Publishers Limited
机译：我们先前将WRAP53确定为调节p53肿瘤抑制因子的反义转录物。 WRAP53基因还编码Cajal体形成所必需的蛋白质，并参与运动神经元复合物，端粒酶和小的Cajal体特异性RNA到Cajal体存活的细胞运输。在这里，我们显示WRAP53蛋白在不同来源的多种癌细胞系中过表达，并且WRAP53过表达促进细胞转化。 WRAP53蛋白的敲低触发了通过线粒体途径的大量凋亡，如Bax / Bak激活，线粒体膜电位丧失和细胞色素c释放所证明的。此外，WRAP53敲低诱导的凋亡可能被Bcl-2过表达所阻断。有趣的是，与正常人细胞相比，人肿瘤细胞对WRAP53耗竭更为敏感，这表明癌细胞特别依赖于WRAP53表达来维持生存。与此相符，我们发现高水平的WRAP53与头颈癌的不良预后相关。这些观察结果共同提出了WRAP53在致癌作用中的作用，并将WRAP53鉴定为大部分恶性肿瘤的新型分子靶标。 2011 Macmillan Publishers Limited

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