Godinho Susana A, Kwon Mijung, Pellman David
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Cancer Metastasis Rev. 2009 Jun;28(1-2):85-98. doi: 10.1007/s10555-008-9163-6.
Precise control of centrosome number is crucial for bipolar spindle assembly and accurate transmission of genetic material to daughter cells. Failure to properly control centrosome number results in supernumerary centrosomes, which are frequently found in cancer cells. This presents a paradox: during mitosis, cells with more than two centrosomes are prone to multipolar mitoses and cell death, however, cancer cells possessing extra centrosomes usually divide successfully. One mechanism frequently utilized by cancer cells to escape death caused by multipolar mitoses is the clustering of supernumerary centrosomes into bipolar arrays. An understanding of the molecular mechanisms by which cancer cells can suppress multipolar mitoses is beginning to emerge. Here, we review what's currently known about centrosome clustering mechanisms and discuss potential strategies to target these mechanisms for the selective killing of cancer cells.
精确控制中心体数量对于双极纺锤体组装以及遗传物质准确传递给子细胞至关重要。未能正确控制中心体数量会导致多余中心体的出现,这在癌细胞中经常可见。这就产生了一个矛盾:在有丝分裂期间,具有两个以上中心体的细胞容易发生多极有丝分裂并导致细胞死亡,然而,拥有额外中心体的癌细胞通常能成功分裂。癌细胞经常利用的一种逃避多极有丝分裂导致的死亡的机制是将多余中心体聚集成双极阵列。对癌细胞能够抑制多极有丝分裂的分子机制的理解正开始浮现。在此,我们综述目前已知的关于中心体聚集机制的知识,并讨论针对这些机制以选择性杀死癌细胞的潜在策略。