Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Box 19, Ness Ziona 7410001, Israel.
J Mol Cell Biol. 2019 Jul 19;11(7):600-604. doi: 10.1093/jmcb/mjz071.
A plethora of studies suggest that the non-transformed cellular and non-cellular components of the tumor, collectively known as the tumor microenvironment, have a significant impact on the tumorigenic process. It was suggested that the microenvironment, which initially restricts tumor development, is recruited by the tumor and maintains a crosstalk that further promotes cancer progression. Indeed, many of the molecules that participate in the tumor-stroma crosstalk have been characterized. However, the crucial factors that are responsible for the initiation of this crosstalk or the 'recruitment' process remain poorly understood. We propose that oncogenes themselves may influence the 'recruitment' of the stromal cells, while focusing on mutant p53. Apart from losing its tumor-suppressing properties, mutant p53 gains novel oncogenic functions, a phenomenon dubbed mutant p53 gain of function (GOF). Here, we discuss possible ways in which mutant p53 may modulate the microenvironment in order to promote tumorigenesis. We thus propose that mutant p53 may serve as a key player in the modulation of the tumor-stroma crosstalk in a way that benefits the tumor. Further elucidation of these 'recruitment' processes, dictated by mutant p53, may be utilized for tailoring personalized therapeutic approaches for patients with tumors that harbor p53 mutation.
大量研究表明，肿瘤的非转化细胞和非细胞成分，统称为肿瘤微环境，对肿瘤发生过程有重大影响。有人提出，最初限制肿瘤发展的微环境被肿瘤招募，并维持着进一步促进癌症进展的串扰。事实上，许多参与肿瘤-基质串扰的分子已经被表征。然而，负责启动这种串扰或“招募”过程的关键因素仍知之甚少。我们提出，癌基因本身可能影响基质细胞的“招募”，同时关注突变型 p53。除了失去其肿瘤抑制特性外，突变型 p53还获得了新的致癌功能，这一现象被称为突变型 p53 获得功能（GOF）。在这里，我们讨论了突变型 p53 可能调节微环境以促进肿瘤发生的几种方式。因此，我们提出突变型 p53 可能在肿瘤-基质串扰的调节中发挥关键作用，从而使肿瘤受益。进一步阐明这些由突变型 p53 决定的“招募”过程，可能被用于为携带 p53 突变的肿瘤患者定制个性化的治疗方法。
