Role of p63 in Development, Tumorigenesis and Cancer Progression
Role of p63 in Development, Tumorigenesis and Cancer Progression
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DOI：
10.1007/s12307-012-0116-9
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发表时间：
2012-12-01
影响因子：
--
通讯作者：
Xiao, Zhi-Xiong
中科院分区：
文献类型：
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作者：
Bergholz, Johann;Xiao, Zhi-Xiong
p53相关蛋白p63具有多效性功能，包括细胞增殖、存活、凋亡、分化、衰老和老化。 p63 基因表达为多种同种型，这些同种型要么包含 N 端 p53 同源反式激活结构域 (TAp63)，要么缺乏该结构域 (Delta Np63)。多项研究表明p63在分层上皮发育中发挥着至关重要的作用，并表明p63对于维持增殖潜力、诱导分化和防止衰老的重要性。此外，许多研究都集中在 p63 在癌症进展中的作用。临床证据表明p63可能在抑制转移中发挥作用。同样，遗传小鼠模型和细胞培养数据强烈表明 p63 缺陷可能是转移扩散的致病因素。而且，p63在癌症转移中的作用已被证明与突变型p53促进癌症恶性的能力有很大关系。然而，对于每种特定异构体的作用仍然存在很多困惑。在这篇综述中，我们重点介绍了当前文献中关于特定 p63 亚型在发育、肿瘤发生，特别是在癌症转移中的作用的一些主要发现。
The p53-related protein p63 has pleiotropic functions, including cell proliferation, survival, apoptosis, differentiation, senescence, and aging. The p63 gene is expressed as multiple isoforms that either contain an N-terminal p53-homologous transactivation domain (TAp63) or that lack this domain (Delta Np63). Multiple studies have demonstrated that p63 plays a crucial role in stratified epithelial development, and have shown the importance of p63 for maintaining proliferation potential, inducing differentiation, and preventing senescence. Additionally, much research focuses on the role of p63 in cancer progression. Clinical evidence suggests that p63 may play a role in inhibiting metastasis. Similarly, genetic mice models together with cell culture data strongly indicate that p63 deficiency may be a causative factor for metastatic spread. Moreover, the role of p63 in cancer metastasis has been shown to be greatly related to the ability of mutant p53 to promote cancer malignancy. However, there is still much confusion as to what the role of each specific isoform is. In this review, we highlight some of the major findings in the current literature regarding the role of specific p63 isoforms in development, tumorigenesis, and particularly in cancer metastasis.