The SOX2-interactome in brain cancer cells identifies the requirement of MSI2 and USP9X for the growth of brain tumor cells.
The SOX2-interactome in brain cancer cells identifies the requirement of MSI2 and USP9X for the growth of brain tumor cells.
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DOI：
10.1371/journal.pone.0062857
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Rizzino A
中科院分区：
文献类型：
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作者：
Cox JL;Wilder PJ;Gilmore JM;Wuebben EL;Washburn MP;Rizzino A
髓母细胞瘤和胶质母细胞瘤分别是儿童和成人最常见的原发性脑肿瘤，治疗极其困难。努力鉴定这些肿瘤生长所必需的新蛋白质可能有助于我们进一步了解这些肿瘤的生物学，以及确定未来治疗的靶点。最近在胚胎干细胞中多个转录因子为中心的蛋白相互作用景观的鉴定已经确定了许多未被研究的蛋白质，这些蛋白质对这些干细胞的自我更新至关重要。为了鉴定对脑肿瘤细胞命运至关重要的新蛋白，我们检测了髓母细胞瘤细胞中转录因子SOX2的蛋白相互作用网络。为此，多维蛋白鉴定技术（MudPIT）在髓母细胞瘤细胞系day中鉴定出>280 sox2相关蛋白。为了开始了解sox2相关蛋白在脑癌中的作用，我们重点研究了两个sox2相关蛋白，武藏2 （MSI2）和泛素特异性蛋白酶9x （USP9X）。最近的研究表明，MSI2（一种假定的RNA结合蛋白）和USP9X（一种去泛素化酶）与几种癌症有关，但与脑肿瘤无关。我们发现，MSI2的下调显著降低了doy细胞以及U87和U118胶质母细胞瘤细胞的生长。我们还发现，在doy、U87和U118脑肿瘤细胞中，USP9X基因的敲低可显著降低肿瘤细胞的生长。总之，我们的研究鉴定了大量的sox2相关蛋白在道y髓母细胞瘤细胞中，并鉴定了两个蛋白，MSI2和USP9X，值得进一步研究，以确定它们是否是脑癌的潜在治疗靶点。
Medulloblastomas and glioblastomas, the most common primary brain tumors in children and adults, respectively, are extremely difficult to treat. Efforts to identify novel proteins essential for the growth of these tumors may help to further our understanding of the biology of these tumors, as well as, identify targets for future therapies. The recent identification of multiple transcription factor-centric protein interaction landscapes in embryonic stem cells has identified numerous understudied proteins that are essential for the self-renewal of these stem cells. To identify novel proteins essential for the fate of brain tumor cells, we examined the protein interaction network of the transcription factor, SOX2, in medulloblastoma cells. For this purpose, Multidimensional Protein Identification Technology (MudPIT) identified >280 SOX2-associated proteins in the medulloblastoma cell line DAOY. To begin to understand the roles of SOX2-associated proteins in brain cancer, we focused on two SOX2-associated proteins, Musashi 2 (MSI2) and Ubiquitin Specific Protease 9x (USP9X). Recent studies have implicated MSI2, a putative RNA binding protein, and USP9X, a deubiquitinating enzyme, in several cancers, but not brain tumors. We demonstrate that knockdown of MSI2 significantly reduces the growth of DAOY cells as well as U87 and U118 glioblastoma cells. We also demonstrate that the knockdown of USP9X in DAOY, U87 and U118 brain tumor cells strongly reduces their growth. Together, our studies identify a large set of SOX2-associated proteins in DAOY medulloblastoma cells and identify two proteins, MSI2 and USP9X, that warrant further investigation to determine whether they are potential therapeutic targets for brain cancer.
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影响因子：
4.1
作者：
Al-Hakim, Abdallah K.;Zagorska, Anna;Alessi, Dario R.
通讯作者：
Alessi, Dario R.
影响因子：
3.6
作者：
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影响因子：
5.3
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通讯作者：
Bernier, Gilbert
影响因子：
5.3
作者：
Imai, T;Tokunaga, A;Okano, H
通讯作者：
Okano, H
影响因子：
82.9
作者：
通讯作者：
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