纺锤体组装检查点在肺癌中的研究进展

Progress in the Study of Spindle Assembly Checkpoint in Lung Cancer

纺锤体组装检查点(spindle assembly checkpoint,SAC)是细胞正确进行有丝分裂(mitosis)的一种保护机制,以防止有丝分裂中后期染色体动粒(kinetochore)存在未附着或不正确附着微管的情况下继续有丝分裂,从而避免整条染色体的增加或丢失而产生非整倍体(aneuploidy)细胞。非整倍体以及SAC组成蛋白的表达改变是不同癌症种类,包括肺癌的共同特征之一。因此,SAC是一种潜在的肺癌治疗新靶点。目前,SAC上游组分蛋白单极纺锤体蛋白激酶1(monopolar spindle 1,MPS1)小分子抑制剂已有5种进入临床试验。本文介绍了SAC的生物学功能,总结了SAC组分蛋白在多种癌症中的表达异常和MPS1抑制剂的研究进展,期望对未来开发靶向SAC组分的肺癌治疗策略提供参考。

Spindle assembly checkpoint(SAC)is a protective mechanism for cells to undergo accurate mitosis.SAC prevented chromosome segregation when kinetochores were not,or incorrectly attached to microtubules in the anaphase of mitosis,thus avoiding aneuploid chromosomes in daughter cells.Aneuploidy and altered expression of SAC component proteins are common in different cancers,including lung cancer.Therefore,SAC is a potential new target for lung cancer therapy.Five small molecule inhibitors of monopolar spindle 1(MPS1),an upstream component protein of SAC,have entered clinical trials.This article introduces the biological functions of SAC,summarizes the abnormal expression of SAC component proteins in various cancers and the research progress of MPS1 inhibitors,and expects to provide a reference for the future development of lung cancer therapeutic strategies targeting SAC components.