Kreis Nina-Naomi, Louwen Frank, Yuan Juping
Department of Gynecology and Obstetrics, University Hospital, J. W. Goethe-University, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany.
Cancers (Basel). 2019 Aug 21;11(9):1220. doi: 10.3390/cancers11091220.
Loss of cell cycle control is characteristic of tumorigenesis. The protein p21 is the founding member of cyclin-dependent kinase inhibitors and an important versatile cell cycle protein. p21 is transcriptionally controlled by p53 and p53-independent pathways. Its expression is increased in response to various intra- and extracellular stimuli to arrest the cell cycle ensuring genomic stability. Apart from its roles in cell cycle regulation including mitosis, p21 is involved in differentiation, cell migration, cytoskeletal dynamics, apoptosis, transcription, DNA repair, reprogramming of induced pluripotent stem cells, autophagy and the onset of senescence. p21 acts either as a tumor suppressor or as an oncogene depending largely on the cellular context, its subcellular localization and posttranslational modifications. In the present review, we briefly mention the general functions of p21 and summarize its roles in differentiation, migration and invasion in detail. Finally, regarding its dual role as tumor suppressor and oncogene, we highlight the potential, difficulties and risks of using p21 as a biomarker as well as a therapeutic target.
细胞周期控制的丧失是肿瘤发生的特征。蛋白质p21是细胞周期蛋白依赖性激酶抑制剂的创始成员，也是一种重要的多功能细胞周期蛋白。p21受p53和非p53途径的转录调控。其表达在响应各种细胞内和细胞外刺激时增加，以阻止细胞周期，确保基因组稳定性。除了在包括有丝分裂在内的细胞周期调控中的作用外，p21还参与分化、细胞迁移、细胞骨架动力学、凋亡、转录、DNA修复、诱导多能干细胞的重编程、自噬和衰老的起始。p21主要根据细胞环境、其亚细胞定位和翻译后修饰，既作为肿瘤抑制因子，也作为癌基因发挥作用。在本综述中，我们简要提及p21的一般功能，并详细总结其在分化、迁移和侵袭中的作用。最后，关于其作为肿瘤抑制因子和癌基因的双重作用，我们强调将p21用作生物标志物以及治疗靶点的潜力、困难和风险。
