Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, Palermo, Italy.
Department of Genetic Stability and Oncogenesis, Institut Gustave Roussy, CNRS UMR8200, 94805, Villejuif, France.
Mol Genet Genomics. 2019 Feb;294(1):149-158. doi: 10.1007/s00438-018-1495-5. Epub 2018 Sep 27.
The spindle assembly checkpoint (SAC) is a cellular surveillance mechanism that ensures the fidelity of chromosomes segregation. Reduced expression of some of its components weakens the SAC and induces chromosome instability and aneuploidy, which are both well-known hallmarks of cancer cells. Centromere protein-E (CENP-E) is a crucial component of the SAC and its function is to facilitate kinetochore microtubule attachment required to achieve and maintain chromosome alignment. The present study investigates the possible role of p14 as a controller of aneuploid cells proliferation. We used RNA interference to induce aneuploidy by partial depletion of CENP-E in human primary fibroblasts (IMR90) and in near diploid tumor cells (HCT116). In contrast to IMR90 aneuploid cell number, which was drastically reduced and leaned towards the WT condition, HCT116 aneuploid cell numbers were slightly decreased at later time points. This euploidy restoration was accompanied by increased p14 expression in IMR90 cells and followed ectopic p14 re-expression in p14-null HCT116 cells. Collectively, our results suggest that hampering proliferation of aneuploid cells could be an additional role of the p14 tumor suppressor.
纺锤体组装检查点（SAC）是一种细胞监控机制，可确保染色体分离的保真度。其某些成分的表达减少会削弱 SAC，并诱导染色体不稳定和非整倍体，这两者都是癌细胞的典型特征。着丝粒蛋白-E（CENP-E）是 SAC 的关键组成部分，其功能是促进有丝分裂纺锤体微管的附着，这是实现和维持染色体对齐所必需的。本研究探讨了 p14 作为非整倍体细胞增殖控制器的可能作用。我们使用 RNA 干扰技术部分耗尽人原代成纤维细胞（IMR90）和近二倍体肿瘤细胞（HCT116）中的 CENP-E 来诱导非整倍体。与 IMR90 非整倍体细胞数量急剧减少并倾向于 WT 条件相反，HCT116 非整倍体细胞数量在稍后的时间点略有减少。这种整倍体恢复伴随着 IMR90 细胞中 p14 表达的增加，并在 p14 缺失的 HCT116 细胞中伴随着异位 p14 重新表达。总之，我们的结果表明，阻碍非整倍体细胞的增殖可能是 p14 肿瘤抑制因子的另一个作用。
