Institut Gustave Roussy, Villejuif, France.
Cell Cycle. 2013 Jan 1;12(1):183-90. doi: 10.4161/cc.23046. Epub 2012 Dec 19.
The illicit generation of tetraploid cells constitutes a prominent driver of oncogenesis, as it often precedes the development of aneuploidy and genomic instability. In addition, tetraploid (pre-)malignant cells display an elevated resistance against radio- and chemotherapy. Here, we report a strategy to preferentially kill tetraploid tumor cells based on the broad-spectrum kinase inhibitor SP600125. Live videomicroscopy revealed that SP600125 affects the execution of mitosis, impedes proper cell division and/or activates apoptosis in near-to-tetraploid, though less so in parental, cancer cells. We propose a novel graphical model to quantify the differential response of diploid and tetraploid cells to mitotic perturbators, including SP600125, which we baptized "transgenerational cell fate profiling." We speculate that this representation constitutes a valid alternative to classical "single-cell fate" and "genealogical" profiling and, hence, may facilitate the analysis of cell fate within a heterogeneous population as well as the visual examination of cell cycle alterations.
四倍体细胞的非法产生是致癌的一个主要驱动因素，因为它通常先于非整倍体和基因组不稳定性的发展。此外，四倍体（前）恶性细胞对放射和化学疗法具有更高的抗性。在这里，我们报告了一种基于广谱激酶抑制剂 SP600125 优先杀死四倍体细胞的策略。实时显微镜观察显示，SP600125 影响有丝分裂的执行，阻碍适当的细胞分裂和/或在近四倍体但在亲本癌细胞中激活细胞凋亡。我们提出了一种新的图形模型来量化二倍体和四倍体细胞对有丝分裂扰动剂（包括 SP600125）的差异反应，我们将其命名为“跨代细胞命运分析”。我们推测这种表示形式是经典的“单细胞命运”和“谱系”分析的有效替代方法，因此可能有助于分析异质群体中的细胞命运以及细胞周期变化的直观检查。
