Institute of Molecular Oncology, Member of the German Center for Lung Research (DZL), Philipps-University, Hans-Meerwein-Straße 3, 35043 Marburg, Germany.
Biomolecules. 2020 Feb 15;10(2):307. doi: 10.3390/biom10020307.
p53 suppresses tumorigenesis by activating a plethora of effector pathways. While most of these operate primarily inside of cells to limit proliferation and survival of incipient cancer cells, many extend to the extracellular space. In particular, p53 controls expression and secretion of numerous extracellular factors that are either soluble or contained within extracellular vesicles such as exosomes. As part of the cellular secretome, they execute key roles in cell-cell communication and extracellular matrix remodeling. Mutations in the p53-encoding gene are the most frequent genetic alterations in cancer cells, and therefore, have profound impact on the composition of the tumor cell secretome. In this review, we discuss how the loss or dominant-negative inhibition of wild-type p53 in concert with a gain of neomorphic properties observed for many mutant p53 proteins, shapes a tumor cell secretome that creates a supportive microenvironment at the primary tumor site and primes niches in distant organs for future metastatic colonization.
p53 通过激活大量效应途径抑制肿瘤发生。虽然这些途径中的大多数主要在细胞内起作用，以限制起始癌细胞的增殖和存活，但许多途径延伸到细胞外空间。特别是，p53 控制着许多细胞外因子的表达和分泌，这些因子要么是可溶性的，要么包含在细胞外囊泡中，如外泌体。作为细胞分泌组的一部分，它们在外细胞间通讯和细胞外基质重塑中发挥关键作用。编码 p53 的基因的突变是癌细胞中最常见的遗传改变，因此对肿瘤细胞分泌组的组成有深远的影响。在这篇综述中，我们讨论了野生型 p53 的缺失或显性抑制与许多突变型 p53 蛋白观察到的新表型特性的协同作用，如何塑造肿瘤细胞分泌组，在原发性肿瘤部位创造一个支持性的微环境，并为远处器官中的龛位进行未来的转移定植做好准备。
