Department of Molecular Cell Biology, The Weizmann Institute of Science, PO Box 26, Rechovot 76100, Israel.
Mol Oncol. 2011 Aug;5(4):315-23. doi: 10.1016/j.molonc.2011.07.007. Epub 2011 Jul 30.
Aneuploidy, often preceded by tetraploidy, is one of the hallmarks of solid tumors. Indeed, both aneuploidy and tetraploidy are oncogenic occurrences that are sufficient to drive neoplastic transformation and cancer progression. True to form, the tumor suppressor p53 obstructs propagation of these dangerous chromosomal events by either instigating irreversible cell cycle arrest or apoptosis. The tumor suppressor Lats2, along with other tumor inhibitory proteins such as BRCA1/2 and BubR1, are central to p53-dependent elimination of tetraploid cells. Not surprisingly, these proteins are frequently inactivated or downregulated in tumors, synergizing with p53 inactivation to establish an atmosphere of "tolerance" for a non-diploid state.
非整倍体，通常先于四倍体出现，是实体瘤的标志之一。事实上，非整倍体和四倍体都是致癌事件，足以驱动肿瘤转化和癌症进展。确实，肿瘤抑制因子 p53 通过引发不可逆的细胞周期停滞或细胞凋亡来阻止这些危险的染色体事件的传播。肿瘤抑制因子 Lats2 与 BRCA1/2 和 BubR1 等其他肿瘤抑制蛋白一起，是 p53 依赖性消除四倍体细胞的核心。毫不奇怪，这些蛋白在肿瘤中经常失活或下调，与 p53 失活协同作用，为非整倍体状态建立“耐受”的氛围。
