纺锤体毒素与细胞命运：两条途径的故事
Spindle poisons and cell fate: a tale of two pathways.
作者信息
Matson Daniel R, Stukenberg P Todd
机构信息
Department of Biochemistry and Molecular Genetics, University of Virginia Medical Center, Charlottesville, VA 22908, USA.
出版信息
Mol Interv. 2011 Apr;11(2):141-50. doi: 10.1124/mi.11.2.12.
Abstract
Spindle poisons, such as paclitaxel and vinblastine, exert their potent anti-neoplastic effects through activation of the spindle assembly checkpoint (SAC), thereby arresting cells in mitosis. Unfortunately, only certain cancers are susceptible to these drugs, and many patients fail to respond to treatment. We review the pathways that are triggered by spindle poisons and highlight recent studies that describe the great variability of tumor cells in responding to these drugs. We also describe the recent identification of an apoptotic pathway that is activated by mitotic arrest in response to spindle poisons. Emerging from these studies is not only a greater understanding of how these classic antimitotic agents bring about cell death, but also a wealth of potential new targets of anticancer therapeutics.
摘要
纺锤体毒素，如紫杉醇和长春花碱，通过激活纺锤体组装检查点（SAC）发挥强大的抗肿瘤作用，从而使细胞停滞在有丝分裂期。不幸的是，只有某些癌症对这些药物敏感，许多患者对治疗没有反应。我们回顾了由纺锤体毒素触发的信号通路，并重点介绍了最近描述肿瘤细胞对这些药物反应存在巨大差异的研究。我们还描述了最近发现的一种凋亡途径，该途径是由纺锤体毒素诱导的有丝分裂停滞激活的。从这些研究中不仅可以更深入地了解这些经典抗有丝分裂药物如何导致细胞死亡，还发现了大量潜在的抗癌治疗新靶点。
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