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	Mps1 kinase regulates tumor cell viability via its novel role in mitochondria
	Zhang, X.1; Ling, Y.2; Guo, Y.1,3; Bai, Y.2; Shi, X.1,3; Gong, F.1,3; Tan, P.1; Zhang, Y.2; Wei, C.2; He, X.2
刊名	Cell death & disease
	2016-07-01
卷号	7页码:12
ISSN号	2041-4889
DOI	10.1038/cddis.2016.193
通讯作者	Xu, q.(xuquanbin73@yahoo.com) ; Ma, r. z.(rlma@genetics.ac.cn)
英文摘要	Targeting mitotic kinase monopolar spindle 1 (mps1) for tumor therapy has been investigated for many years. although it was suggested that mps1 regulates cell viability through its role in spindle assembly checkpoint (sac), the underlying mechanism remains less defined. in an endeavor to reveal the role of high levels of mitotic kinase mps1 in the development of colon cancer, we unexpectedly found the amount of mps1 required for cell survival far exceeds that of maintaining sac in aneuploid cell lines. this suggests that other functions of mps1 besides sac are also employed to maintain cell viability. mps1 regulates cell viability independent of its role in cytokinesis as the genetic depletion of mps1 spanning from metaphase to cytokinesis affects neither cytokinesis nor cell viability. furthermore, we developed a single-cycle inhibition strategy that allows disruption of mps1 function only in mitosis. using this strategy, we found the functions of mps1 in mitosis are vital for cell viability as short-term treatment of mitotic colon cancer cell lines with mps1 inhibitors is sufficient to cause cell death. interestingly, mps1 inhibitors synergize with microtubule depolymerizing drug in promoting polyploidization but not in tumor cell growth inhibition. finally, we found that mps1 can be recruited to mitochondria by binding to voltage-dependent anion channel 1 (vdac1) via its c-terminal fragment. this interaction is essential for cell viability as mps1 mutant defective for interaction fails to main cell viability, causing the release of cytochrome c. meanwhile, deprivation of vdac1 can make tumor cells refractory to loss of mps1-induced cell death. collectively, we conclude that inhibition of the novel mitochondrial function mps1 is sufficient to kill tumor cells.
WOS关键词	SPINDLE ASSEMBLY CHECKPOINT ; DEPENDENT ANION CHANNELS ; SMALL-MOLECULE INHIBITOR ; MITOTIC CHECKPOINT ; CHROMOSOME MISSEGREGATION ; MAMMALIAN-CELLS ; CANCER-CELLS ; CENTROSOME DUPLICATION ; PROTEIN-KINASES ; TARGETING MPS1
WOS研究方向	Cell Biology
WOS类目	Cell Biology
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000380920200027
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2375131
专题	中国科学院大学
通讯作者	Xu, Q.; Ma, R. Z.
作者单位	1.Chinese Acad Sci, Inst Genet & Dev Biol, State Key Lab Mol Dev Biol, Beijing 100101, Peoples R China 2.Beijing Inst Biotechnol, Beijing 100850, Peoples R China 3.Univ Chinese Acad Sci, Grad Sch, Beijing 100149, Peoples R China 4.Univ Colorado, Boulder, CO 80302 USA
推荐引用方式 GB/T 7714	Zhang, X.,Ling, Y.,Guo, Y.,et al. Mps1 kinase regulates tumor cell viability via its novel role in mitochondria[J]. Cell death & disease,2016,7:12.
APA	Zhang, X..,Ling, Y..,Guo, Y..,Bai, Y..,Shi, X..,...&Ma, R. Z..(2016).Mps1 kinase regulates tumor cell viability via its novel role in mitochondria.Cell death & disease,7,12.
MLA	Zhang, X.,et al."Mps1 kinase regulates tumor cell viability via its novel role in mitochondria".Cell death & disease 7(2016):12.

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