Chromosomal instability (CIN) is a hallmark of cancer, resulting from misalignment and missegregation of chromosomes during meta- and anaphase, due to non-precise regulation of spindle-MT dynamics. Diaphanous Related Formin 1 (DIAPH1) is an actin nucleator and also binds microtubule (MT) with high affinity. In this study, we analyzed the role of DIAPH1 in regulation of spindle MT-dynamics and CIN in HT29 and HCT-116 colorectal cancer (CRC) cells. Our data show that down-regulation of DIAPH1 in these cell lines decreased spindle-MT speed by 50 % and the fraction of cells with misaligned and missegregated chromosomes was significantly increased. Furthermore, in HCT-116 DIAPH1 depleted cells deviation of chromosome number was elevated and the number of cells with micronuclei and cytosolic DNA was increased in both DIAPH1-knock down cell lines. In line with these results, database analysis revealed a significant correlation with low DIAPH1 mRNA expression and aneuploidy. Thus, DIAPH1 is substantially involved in the control of CIN in CRC cells. Since in vitro, DIAPH1 directly increased MT-polymerization, we assume that DIAPH1 controls CIN by regulating spindle-MT dynamics.

染色体不稳定性 (CIN) 是癌症的一个标志，由于对纺锤体 MT 动力学的不精确调节，导致中期和后期染色体的错位和错误分离。透明相关形式 1 (DIAPH1) 是一种肌动蛋白成核剂，并且还以高亲和力结合微管 (MT)。在这项研究中，我们分析了 DIAPH1 在调节 HT29 和 HCT-116 结直肠癌 (CRC) 细胞中纺锤体 MT 动力学和 CIN 中的作用。我们的数据显示，这些细胞系中 DIAPH1 的下调使纺锤体-MT 速度降低了 50%，并且染色体未对齐和错误分离的细胞比例显着增加。此外，在 HCT-116 中，DIAPH1 耗尽的细胞染色体数量偏差升高，并且在两种 DIAPH1 敲低细胞系中，具有微核和胞质 DNA 的细胞数量增加。与这些结果一致，数据库分析揭示了与低 DIAPH1 mRNA 表达和非整倍体的显着相关性。因此，DIAPH1 实质上参与了 CRC 细胞中 CIN 的控制。自从在体外，DIAPH1 直接增加了 MT 聚合，我们假设 DIAPH1 通过调节纺锤体-MT 动力学来控制 CIN。