OTUB1 de-ubiquitinating enzyme promotes prostate cancer cell invasion in vitro and tumorigenesis in vivo.
OTUB1 de-ubiquitinating enzyme promotes prostate cancer cell invasion in vitro and tumorigenesis in vivo.
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DOI：
10.1186/s12943-014-0280-2
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发表时间：
2015-01-27
期刊：
影响因子：
37.3
通讯作者：
Flores-Morales A
中科院分区：
文献类型：
--
作者：
Iglesias-Gato D;Chuan YC;Jiang N;Svensson C;Bao J;Paul I;Egevad L;Kessler BM;Wikström P;Niu Y;Flores-Morales A
泛素化是一个高度动态和可逆的过程，在细胞稳态中发挥着核心作用。几种去泛素化酶的失调与肿瘤的发展有关，但它们在前列腺癌进展中的具体作用仍有待探索。 RNAi筛选用于研究去泛素化酶的卵巢肿瘤蛋白酶（OTU）家族对前列腺癌细胞增殖和侵袭能力的作用。测量 RhoA 活性与 OTUB1 对前列腺癌细胞侵袭的影响相关。使用具有稳定 OTUB1 敲低的肿瘤异种移植小鼠模型来研究 OTUB1 对肿瘤生长的影响。我们的 RNAi 筛选发现 OTUB1 通过调节 RhoA 激活是前列腺癌细胞侵袭的重要调节因子。 OTUB1 对 RhoA 激活的影响对于雄激素诱导的前列腺癌细胞 p53 表达抑制非常重要。在局部前列腺癌肿瘤中，与正常前列腺上皮细胞相比，OTUB1 过度表达。表达降低水平的 OTUB1 的前列腺癌异种移植物表现出肿瘤生长减少和体内转移扩散减少。 OTUB1通过RhoA激活介导前列腺癌细胞侵袭并促进体内肿瘤发生。我们的结果表明，针对 OTUB1 催化活性的药物有可能用作转移性前列腺癌的治疗药物。本文的在线版本 (doi:10.1186/s12943-014-0280-2) 包含补充材料，可供授权用户使用。
Ubiquitination is a highly dynamic and reversible process with a central role in cell homeostasis. Deregulation of several deubiquitinating enzymes has been linked to tumor development but their specific role in prostate cancer progression remains unexplored. RNAi screening was used to investigate the role of the ovarian tumor proteases (OTU) family of deubiquitinating enzymes on the proliferation and invasion capacity of prostate cancer cells. RhoA activity was measured in relation with OTUB1 effects on prostate cancer cell invasion. Tumor xenograft mouse model with stable OTUB1 knockdown was used to investigate OTUB1 influence in tumor growth. Our RNAi screening identified OTUB1 as an important regulator of prostate cancer cell invasion through the modulation of RhoA activation. The effect of OTUB1 on RhoA activation is important for androgen-induced repression of p53 expression in prostate cancer cells. In localized prostate cancer tumors OTUB1 was found overexpressed as compared to normal prostatic epithelial cells. Prostate cancer xenografts expressing reduced levels of OTUB1 exhibit reduced tumor growth and reduced metastatic dissemination in vivo. OTUB1 mediates prostate cancer cell invasion through RhoA activation and promotes tumorigenesis in vivo. Our results suggest that drugs targeting the catalytic activity of OTUB1 could potentially be used as therapeutics for metastatic prostate cancer. The online version of this article (doi:10.1186/s12943-014-0280-2) contains supplementary material, which is available to authorized users.
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影响因子：
2.1
作者：
Crawford, E. David
通讯作者：
Crawford, E. David
影响因子：
4.4
作者：
Cox, Juergen;Neuhauser, Nadin;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
6.4
作者：
Kluth, Martina;Harasimowicz, Silvia;Schlomm, Thorsten
通讯作者：
Schlomm, Thorsten
影响因子：
--
作者：
Gonzalez-Montelongo, Maria C.;Marin, Raquel;Diaz, Mario
通讯作者：
Diaz, Mario
影响因子：
8
作者：
Chuan, Y-C;Iglesias-Gato, D.;Flores-Morales, A.
通讯作者：
Flores-Morales, A.