Li Yi, Zhang Meng-Chen, Xu Xiao-Kang, Zhao Yang, Mahanand Chatoo, Zhu Tao, Deng Hong, Nevo Eviatar, Du Ji-Zeng, Chen Xue-Qun
Division of Neurobiology and Physiology, Department of Basic Medical Sciences, School of Medicine, Zhejiang University HHangzhou, China.
Department of Biology, University of Rochester, Rochester, NY, United States.
Front Endocrinol (Lausanne). 2019 Mar 12;10:152. doi: 10.3389/fendo.2019.00152. eCollection 2019.
The common understanding of p53 function is a genome guardian, which is activated by diverse stresses stimuli and mediates DNA repair, apoptosis, and cell cycle arrest. Increasing evidence has demonstrated p53 new cellular functions involved in abundant endocrine and metabolic response for maintaining homeostasis. However, is frequently mutant in human cancers, and the mutant p53 (Mut-p53) turns to an "evil" cancer-assistant. Mut-p53-induced epithelial-mesenchymal transition (EMT) plays a crucial role in the invasion and metastasis of endocrine carcinomas, and Mut-p53 is involved in cancer immune evasion by upregulating PD-L1 expression. Therefore, Mut-p53 is a valuable treatment target for malignant tumors. Targeting Mut-p53 in correcting sequence and conformation are increasingly concerned. Interestingly, in wild animals, p53 variations contribute to cancer resistant and high longevity. This review has discussed the multiple functions of p53 in health, diseases, and nature evolution, summarized the frequently mutant sites of p53, and the mechanisms of Mut-p53-mediated metastasis and immune evasion in endocrine cancers. We have provided a new insight for multiple roles of p53 in human and wild animals.
对p53功能的普遍理解是它作为基因组守护者，被多种应激刺激激活，并介导DNA修复、细胞凋亡和细胞周期阻滞。越来越多的证据表明，p53在维持体内平衡的丰富内分泌和代谢反应中具有新的细胞功能。然而，p53在人类癌症中经常发生突变，突变型p53（Mut-p53）变成了一个“邪恶”的癌症辅助因子。Mut-p53诱导的上皮-间质转化（EMT）在内分泌癌的侵袭和转移中起关键作用，并且Mut-p53通过上调PD-L1表达参与癌症免疫逃逸。因此，Mut-p53是恶性肿瘤的一个有价值的治疗靶点。针对Mut-p53校正序列和构象的研究越来越受到关注。有趣的是，在野生动物中，p53变异有助于抗癌和长寿。本文综述了p53在健康、疾病和自然进化中的多种功能，总结了p53的常见突变位点，以及Mut-p53在内分泌癌中介导转移和免疫逃逸的机制。我们为p53在人类和野生动物中的多种作用提供了新的见解。
