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了解p53:肿瘤抑制的新见解。

Understanding p53: new insights into tumor suppression.

作者信息

Kawauchi Keiko, Wolf Steven John

机构信息

Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, 7-1-20 Minatojima-minamimachi, Kobe, Hyogo 650-0047, Japan.

出版信息

Expert Rev Anticancer Ther. 2014 Oct;14(10):1101-3. doi: 10.1586/14737140.2014.948859. Epub 2014 Aug 14.

Abstract

p53 (aka TP53) is a powerful tumor suppressor, and oncogenic transformation is induced when the ability of p53 to suppress tumorigenesis is compromised. p53 not only prevents tumorigenesis, but also tumor progression, that is, local invasion and distant metastasis. Recently, we showed that cytoplasmic p53 prevents RAS-driven invasion via alteration of actin cytoskeleton remodeling. This follows modulation of mitochondrial integrity. The transcriptional activity of p53 has been restored using small molecules; however, their success as cancer therapies is largely dependent on the status of downstream targets of p53. It is therefore important to elucidate the role of these downstream targets in p53 regulated tumor progression. With the recently described mechanism of tumor suppression highlighting a role of p53's downstream targets in the regulation of actin cytoskeleton dynamics and lamellipodia formation, we suggest that potential therapeutic targets may be revealed within this mechanism that can be exploited in anticancer therapy.

摘要

p53(又称TP53)是一种强大的肿瘤抑制因子,当p53抑制肿瘤发生的能力受损时,就会诱导致癌转化。p53不仅能预防肿瘤发生,还能阻止肿瘤进展,即局部侵袭和远处转移。最近,我们发现细胞质中的p53通过改变肌动蛋白细胞骨架重塑来阻止RAS驱动的侵袭。这是在调节线粒体完整性之后发生的。已经使用小分子恢复了p53的转录活性;然而,它们作为癌症治疗方法的成功很大程度上取决于p53下游靶点的状态。因此,阐明这些下游靶点在p53调节的肿瘤进展中的作用非常重要。随着最近描述的肿瘤抑制机制突出了p53下游靶点在调节肌动蛋白细胞骨架动力学和片状伪足形成中的作用,我们认为在这一机制中可能会揭示出可用于抗癌治疗的潜在治疗靶点。

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