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突变型p53在转移进程中的作用

Mutant p53 on the Path to Metastasis.

作者信息

Tang Qiaosi, Su Zhenyi, Gu Wei, Rustgi Anil K

机构信息

Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032, USA.

Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032, USA.

出版信息

Trends Cancer. 2020 Jan;6(1):62-73. doi: 10.1016/j.trecan.2019.11.004. Epub 2019 Dec 16.

Abstract

Metastasis contributes to the vast majority of cancer-related mortality. Regulatory mechanisms of the multistep invasion-metastasis cascade are being unraveled. TP53 is the most frequently mutated gene across human cancers. Accumulating evidence has shown that mutations of TP53 not only lead to loss of function or dominant negative effects, but also promotes a gain of function. Specifically, gain of function mutant p53 promotes cancer cell motility, invasion, and metastasis. Here, we summarize the mechanisms and functions of mutant p53 that foster metastasis in different types of cancers. We also discuss the prognostic value of mutant p53 and current status of therapeutic strategies targeting mutant p53. Future studies will shed light on discovering novel mechanisms of mutant p53-driven cancer metastasis and developing innovative therapeutics to improve clinical outcomes in patients harboring p53 mutations.

摘要

转移是导致绝大多数癌症相关死亡的原因。多步骤侵袭转移级联反应的调控机制正在被逐步阐明。TP53是人类癌症中最常发生突变的基因。越来越多的证据表明,TP53突变不仅会导致功能丧失或显性负效应,还会促进功能获得。具体而言,功能获得性突变型p53会促进癌细胞的运动、侵袭和转移。在此,我们总结了突变型p53在不同类型癌症中促进转移的机制和功能。我们还讨论了突变型p53的预后价值以及针对突变型p53的治疗策略的现状。未来的研究将有助于发现突变型p53驱动癌症转移的新机制,并开发创新疗法以改善携带p53突变患者的临床结局。

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