Pérez de Castro Ignacio, Malumbres Marcos
Cell Division and Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Genes Cancer. 2012 Nov;3(11-12):721-30. doi: 10.1177/1947601912473306.
Cell cycle deregulation is a common motif in human cancer, and multiple therapeutic strategies are aimed to prevent tumor cell proliferation. Whereas most current therapies are designed to arrest cell cycle progression either in G1/S or in mitosis, new proposals include targeting the intrinsic chromosomal instability (CIN, an increased rate of gain or losses of chromosomes during cell division) or aneuploidy (a genomic composition that differs from diploid) that many tumor cells display. Why tumors cells are chromosomally unstable or aneuploid and what are the consequences of these alterations are not completely clear at present. Several mitotic regulators are overexpressed as a consequence of oncogenic alterations, and they are likely to alter the proper regulation of chromosome segregation in cancer cells. In this review, we propose the relevance of TPX2, a mitotic regulator involved in the formation of the mitotic spindle, in oncogene-induced mitotic stress. This protein, as well as its partner Aurora-A, is frequently overexpressed in human cancer, and its deregulation may participate not only in chromosome numeric aberrations but also in other forms of genomic instability in cancer cells.
细胞周期失调是人类癌症中的一个常见特征，多种治疗策略旨在阻止肿瘤细胞增殖。虽然目前大多数疗法旨在使细胞周期进程在G1/S期或有丝分裂期停滞，但新的方案包括针对许多肿瘤细胞所表现出的内在染色体不稳定性（CIN，细胞分裂过程中染色体获得或丢失速率增加）或非整倍体（与二倍体不同的基因组组成）。目前尚不完全清楚肿瘤细胞为何染色体不稳定或为非整倍体，以及这些改变会带来何种后果。一些有丝分裂调节因子由于致癌改变而过度表达，它们可能会改变癌细胞中染色体分离的正常调控。在本综述中，我们提出了TPX2（一种参与有丝分裂纺锤体形成的有丝分裂调节因子）在癌基因诱导的有丝分裂应激中的相关性。这种蛋白质及其伴侣Aurora-A在人类癌症中经常过度表达，其失调不仅可能参与染色体数目畸变，还可能参与癌细胞中其他形式的基因组不稳定。
