Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovat, Israel.
Cancer Gene Ther. 2011 Jan;18(1):2-11. doi: 10.1038/cgt.2010.63. Epub 2010 Oct 22.
Three decades of p53 research have led to many advances in understanding the basic biology of normal and cancer cells. Nonetheless, the detailed functions of p53 in normal cells, and even more so in cancer cells, remain obscure. A major breakthrough is the realization that mutant p53 has a life of its own: it contributes to cancer not only through loss of activity, but also through gain of specific 'mutant functions'. This new focus on mutant p53 is the rationale behind the meeting series dedicated to advances on mutant p53 biology. This review provides an overview of results presented at the Fourth International Workshop on Mutant p53, held in Akko, Israel in March 2009. New roles and functions of p53 relevant for tumor suppressions were presented, including the regulation of microRNAs networks, the modulation of cell-stroma interactions and the induction of senescence. A main focus of the meeting was the rapidly growing body of knowledge on autonomous properties of mutant p53 and on their oncogenic 'gain of function' impact. Importantly, the meeting highlighted that, 30 years after p53 discovery, research on mutant p53 is entering the clinical and translational era. Two major steps forward in this respect are a better understanding of the active mechanism of small drugs targeting mutant p53 in tumor cells and an improved definition of the prognostic and predictive value of mutant p53 in human cancer.
三十年来的 p53 研究促进了人们对正常细胞和癌细胞基本生物学的理解。尽管如此，p53 在正常细胞中的详细功能，甚至在癌细胞中，仍然不清楚。一个重大突破是认识到突变型 p53 有其自身的生命：它不仅通过丧失活性，而且通过获得特定的“突变功能”来促进癌症。这种对突变型 p53 的新关注是专门针对突变型 p53 生物学进展的会议系列的基础。这篇综述概述了 2009 年 3 月在以色列阿科举行的第四届国际突变 p53 研讨会上提交的结果。介绍了与肿瘤抑制相关的 p53 的新作用和功能，包括 microRNAs 网络的调节、细胞-基质相互作用的调节和衰老的诱导。会议的一个主要重点是关于突变型 p53 的自主特性及其致癌“获得功能”影响的知识的快速增长。重要的是，会议强调，p53 发现 30 年后，突变型 p53 的研究正在进入临床和转化时代。在这方面向前迈出的两大步是更好地理解针对肿瘤细胞中突变型 p53 的小分子药物的作用机制，以及更好地定义突变型 p53 在人类癌症中的预后和预测价值。
