Ezrin mediates c-Myc actions in prostate cancer cell invasion
Ezrin mediates c-Myc actions in prostate cancer cell invasion
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DOI：
10.1038/onc.2009.442
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发表时间：
2010-03-01
期刊：
影响因子：
8
通讯作者：
Flores-Morales, A.
中科院分区：
文献类型：
--
作者：
Chuan, Y-C;Iglesias-Gato, D.;Flores-Morales, A.
小鼠前列腺和正常人前列腺上皮细胞中c-Myc的强制过表达导致具有侵袭性表型的肿瘤转化。c-Myc如何调节细胞侵袭还知之甚少。在这项研究中，我们研究了c-Myc和雄激素在前列腺癌细胞侵袭调节中的相互作用。我们发现，c-Myc诱导细胞侵袭和锚定非依赖性的增长，通过调节ezrin蛋白的表达，在雄激素的存在下。ezrin启动子的活性由雄激素通过c-Myc控制，c-Myc结合位于近端启动子区域的遗传学保守的E-Box。此外，我们还表明ezrin是c-Myc蛋白水平的重要调节剂。这些作用是通过雄激素诱导的ezrin磷酸化的变化来实现的，这导致下游信号的调节。这些下游信号涉及Akt和GSK-3 β活性的调节，导致c-Myc蛋白合成增加并抑制其降解。总之，我们已经证明了埃兹蛋白作为c-Myc诱导的前列腺癌细胞肿瘤发生的介导剂的关键作用。Oncogene（2010）29，1531-1542; doi：10.1038/onc.2009.442; 2009年12月14日在线发表
The forced overexpression of c-Myc in mouse prostate and in normal human prostate epithelial cells results in tumor transformation with an invasive phenotype. How c-Myc regulates cell invasion is poorly understood. In this study, we have investigated the interplay of c-Myc and androgens in the regulation of prostate cancer cell invasion. We found that c-Myc induces cell invasion and anchorage-independent growth by regulating ezrin protein expression in the presence of androgens. The activity of the ezrin promoter is controlled by androgens through c-Myc, which binds to a phylogenetically conserved E-Box located in the proximal promoter region. Besides, we also show that ezrin is an important regulator of c-Myc protein levels. These effects are achieved through androgen-induced changes in ezrin phosphorylation, which results in the regulation of downstream signals. These downstream signals involve the modulation of Akt and GSK-3 beta activity resulting in increased c-Myc protein synthesis and inhibition of its degradation. In summary, we have shown a key role for ezrin as a mediator of c-Myc-induced tumorigenesis in prostate cancer cells. Oncogene (2010) 29, 1531-1542; doi:10.1038/onc.2009.442; published online 14 December 2009