Lin Xinrong, Xiang Xiaosong, Hao Liping, Wang Ting, Lai Yongting, Abudoureyimu Mubalake, Zhou Hao, Feng Bing, Chu Xiaoyuan, Wang Rui
Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University Nanjing, China.
Affiliated Jinling Hospital Research Institution of General Surgery, Medical School of Nanjing University Nanjing, China.
Am J Cancer Res. 2020 Sep 1;10(9):2705-2729. eCollection 2020.
Aurora-A is a mitotic serine/threonine-protein kinase and an oncogene. In normal cells, Aurora-A appears from G2 phase and localizes at the centrosome, where it participates in centrosome replication, isolation and maturation. Aurora-A also maintains Golgi apparatus structure and spindle assembly. Aurora-A undergoes ubiquitination-mediated degradation after the cell division phase. Aurora-A is abnormally expressed in tumor cells and promotes cell proliferation by regulating mitotic substrates, such as PP1, PLK1, TPX2, and LAST2, and affects other molecules through a non-mitotic pathway to promote cell invasion and metastasis. Some molecules in tumor cells also indirectly act on Aurora-A to regulate tumor cells. Aurora-A also mediates resistance to chemotherapy and radiotherapy and is involved in tumor immunotherapy. Clinical trials of Aurora-A molecular inhibitors are currently underway, and clinical transformation is just around the corner.
Aurora-A是一种有丝分裂丝氨酸/苏氨酸蛋白激酶,也是一种癌基因。在正常细胞中,Aurora-A从G2期出现并定位于中心体,在那里它参与中心体的复制、分离和成熟。Aurora-A还维持高尔基体结构和纺锤体组装。Aurora-A在细胞分裂期后经历泛素化介导的降解。Aurora-A在肿瘤细胞中异常表达,通过调节有丝分裂底物如PP1、PLK1、TPX2和LAST2促进细胞增殖,并通过非有丝分裂途径影响其他分子以促进细胞侵袭和转移。肿瘤细胞中的一些分子也间接作用于Aurora-A以调节肿瘤细胞。Aurora-A还介导对化疗和放疗的耐药性,并参与肿瘤免疫治疗。目前正在进行Aurora-A分子抑制剂的临床试验,临床转化即将到来。