Inhibition of gliomagenesis and attenuation of mitotic transition by MIIP
Inhibition of gliomagenesis and attenuation of mitotic transition by MIIP
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DOI：
10.1038/onc.2010.114
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发表时间：
2010-06-17
期刊：
影响因子：
8
通讯作者：
Zhang, W.
中科院分区：
文献类型：
--
作者：
Ji, P.;Smith, S. M.;Zhang, W.
迁移和侵袭抑制蛋白(MIIP，又称IIp45)是胶质瘤中细胞迁移和侵袭的负性调节因子。我们以前的研究表明，在从胶质母细胞瘤患者获得的一些组织样本中，MIIP蛋白减少或检测不到。MIIP在胶质瘤发生中的意义尚不清楚。在这项研究中，我们报道了MIIP在抑制胶质瘤形成和抑制有丝分裂转变方面发挥了重要作用。MIIP表达水平的增加抑制了胶质瘤细胞系的集落形成和细胞生长，而针对MIIP的特异性小干扰RNA降低了MIIP的表达水平，从而促进了细胞的生长。在胶质细胞特异的小鼠模型中，MIIP的表达抑制了胶质瘤的发展和进展，从而表明MIIP是一种胶质瘤形成的抑制因子。此外，我们发现MIIP减弱了有丝分裂的转变，并导致了有丝分裂灾难的增加。MIIP在这一过程中的生化机制与其对后期促进复合体(APC/C)活性的调节有关。MIIP与CDC20直接相互作用，MIIP与CDC20的相互作用抑制APC/C介导的细胞周期蛋白B1的降解。因此，MIIP减弱了有丝分裂的转变，增加了有丝分裂的灾难，从而抑制了胶质瘤的发展和进展。Oncogene(2010)29,3501-3508；doi：10.1038/onc.2010.114；2010年4月26日在线发布
The migration and invasion inhibitor protein (MIIP, also known as IIp45) was discovered as a negative regulator of cell migration and invasion in glioma. Our previous studies have shown that the MIIP protein was reduced or undetectable in some tissue samples obtained from patients with glioblastoma. The significance of MIIP in gliomagenesis is unknown. In this study, we report that MIIP has an important role in the inhibition of gliomagenesis and attenuation of mitotic transition. Increased MIIP expression levels inhibited colony formation and cell growth of glioma cell lines in vitro, whereas decreased expression by specific small interfering RNA for MIIP resulted in increased cell growth. Expression of MIIP in a glial-specific mouse model blocked glioma development and progression, thus showing that MIIP is an inhibitor of gliomagenesis. Furthermore, we show that MIIP attenuates mitotic transition and results in increased mitotic catastrophe. The biochemical mechanism of MIIP in this process is associated with its regulation of anaphase-promoting complex (APC/C) activity. MIIP interacts directly with Cdc20, and the interaction of MIIP with Cdc20 inhibits APC/C-mediated degradation of cyclin B1. Thus, MIIP attenuates mitotic transition and increases mitotic catastrophe, thereby inhibiting glioma development and progression. Oncogene (2010) 29, 3501-3508; doi:10.1038/onc.2010.114; published online 26 April 2010