Institute of Molecular Biology and Pathology, National Research Council of Italy, c/o Sapienza University of Rome, Rome, Italy.
Department of Biochemical Sciences, Sapienza University of Rome, Rome, Italy.
Oncogene. 2021 Jun;40(23):3917-3928. doi: 10.1038/s41388-021-01766-w. Epub 2021 May 13.
The Aurora-A kinase regulates cell division, by controlling centrosome biology and spindle assembly. Cancer cells often display elevated levels of the kinase, due to amplification of the gene locus, increased transcription or post-translational modifications. Several inhibitors of Aurora-A activity have been developed as anti-cancer agents and are under evaluation in clinical trials. Although the well-known mitotic roles of Aurora-A point at chromosomal instability, a hallmark of cancer, as a major link between Aurora-A overexpression and disease, recent evidence highlights the existence of non-mitotic functions of potential relevance. Here we focus on a nuclear-localised fraction of Aurora-A with oncogenic roles. Interestingly, this pool would identify not only non-mitotic, but also kinase-independent functions of the kinase. We review existing data in the literature and databases, examining potential links between Aurora-A stabilisation and localisation, and discuss them in the perspective of a more effective targeting of Aurora-A in cancer therapy.
极光激酶 A 通过控制中心体生物学和纺锤体组装来调节细胞分裂。由于基因座扩增、转录增加或翻译后修饰，癌细胞中激酶的水平常常升高。已经开发出几种极光激酶 A 活性的抑制剂作为抗癌药物，并正在临床试验中进行评估。尽管极光激酶 A 的众所周知的有丝分裂作用指向了癌症的一个标志，即染色体不稳定性，但最近的证据强调了其过度表达与疾病之间存在非有丝分裂功能的潜在联系。在这里，我们关注具有致癌作用的极光激酶 A 的核定位部分。有趣的是，这个池不仅可以识别非有丝分裂，还可以识别激酶非依赖性的激酶功能。我们回顾了文献和数据库中的现有数据，研究了极光激酶 A 稳定化和定位之间的潜在联系，并从更有效地靶向癌症治疗中的极光激酶 A 的角度对其进行了讨论。
