Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, Taiwan.
Cell Cycle. 2012 Mar 1;11(5):934-52. doi: 10.4161/cc.11.5.19452.
Centrosome amplification and chromosome abnormality are frequently identified in neoplasia and tumorigenesis. However, the mechanisms underlying these defects remain unclear. We here identify that MCT-1 is a centrosomal oncoprotein involved in mitosis. Knockdown of MCT-1 protein results in intercellular bridging, chromosome mis-congregation, cytokinesis delay, and mitotic death. Introduction of MCT-1 oncogene into the p53 deficient cells (MCT-1-p53), the mitotic checkpoint kinases and proteins are deregulated synergistically. These biochemical alterations are accompanied with increased frequencies of cytokinesis failure, multi-nucleation, and centrosome amplification in subsequent cell cycle. As a result, the incidences of polyploidy and aneuploidy are progressively induced by prolonged cell cultivation or further promoted by sustained spindle damage on MCT-1-p53 background. These data show that the oncoprotein perturbs centrosome structure and mitotic progression, which provide the molecular aspect of chromsomal abnormality in vitro and the information for understanding the stepwise progression of tumors under oncogenic stress.
中心体扩增和染色体异常在肿瘤发生中经常被发现。然而，这些缺陷的机制仍不清楚。我们在这里发现 MCT-1 是一种参与有丝分裂的中心体癌蛋白。MCT-1 蛋白的敲低导致细胞间桥接、染色体错误聚集、胞质分裂延迟和有丝分裂死亡。将 MCT-1 癌基因导入 p53 缺陷细胞（MCT-1-p53）中，有丝分裂检查点激酶和蛋白协同失调。这些生化改变伴随着细胞周期中胞质分裂失败、多核和中心体扩增的频率增加。结果，随着细胞培养时间的延长或在 MCT-1-p53 背景下持续的纺锤体损伤进一步促进，多倍体和非整倍体的发生率逐渐增加。这些数据表明，癌蛋白扰乱了中心体结构和有丝分裂进程，为体外染色体异常提供了分子方面的信息，并为理解致癌应激下肿瘤的逐步进展提供了信息。
