Role of small ubiquitin-like modifier proteins-1 (SUMO-1) in regulating migration and invasion of fibroblast-like synoviocytes from patients with rheumatoid arthritis.
Role of small ubiquitin-like modifier proteins-1 (SUMO-1) in regulating migration and invasion of fibroblast-like synoviocytes from patients with rheumatoid arthritis.
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小泛素样修饰蛋白 1 (SUMO-1) 在调节类风湿性关节炎患者成纤维细胞样滑膜细胞迁移和侵袭中的作用。
DOI：
10.1016/j.yexcr.2018.12.011
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发表时间：
2019-02
期刊：
影响因子：
--
通讯作者：
Xu H
中科院分区：
文献类型：
--
作者：
Lao M;Zhan Z;Li N;Xu S;Shi M;Zou Y;Huang M;Zeng S;Liang L;Xu H
类风湿性关节炎(RA)的特征是软骨侵蚀和骨质破坏。成纤维样滑膜细胞的侵袭性增强在这一过程中起着至关重要的作用。小泛素样修饰物(SUMO)蛋白包括相扑-1、相扑-2、相扑-3和相扑-4，在一些细胞系中参与调节许多细胞事件，如生存、迁移和信号转导。然而，它们在类风湿关节炎发病机制中的作用还不是很清楚。因此，我们评估了SUMO蛋白在RA FLSS迁移和侵袭中的作用。我们发现，在RA患者的FLSS和滑膜组织中，SUMO-1和SUMO-2的表达均升高。小干扰RNA(SiRNA)抑制SUMO-1可减少RA Fls的迁移和侵袭，并减少MMP1和MMP3表达。我们还证明了在细胞迁移过程中，SUMO-1调控片状磷脂的形成。为了进一步探讨分子机制，我们评估了SUMO-1基因敲除对控制细胞运动的关键信号通路rac1/PAK1激活的影响。我们的结果表明，SUMO-1介导的SUMO化作用控制了rac1的激活，并调节了下游的PAK1活性。抑制rac1或PAK1也可减少RA Fls的迁移和侵袭。我们的发现表明，抑制相扑-1可能通过抑制RA FLSS的攻击行为来保护RA免受关节破坏。
Rheumatoid arthritis (RA) is featured by erosive cartilage and bone destruction. The enhancing aggressive property of fibroblast-like synoviocytes (FLSs) plays a critical role in this process. Small ubiquitin-like modifier (SUMO) proteins, including SUMO-1, SUMO-2, SUMO-3 and SUMO-4, participate in regulating many cellular events such as survival, migration and signal transduction in some cell lines. However, their roles in the pathogenesis of RA are not well established. Therefore, we evaluated the role of SUMO proteins in RA FLSs migration and invasion. We found that expression of both SUMO-1 and SUMO-2 was elevated in FLSs and synovial tissues (STs) from patients with RA. SUMO-1 suppression by small interference RNA (siRNA) reduced migration and invasion as well as MMP-1 and MMP-3 expression in RA FLSs. We also demonstrated that SUMO-1 regulated lamellipodium formation during cell migration. To explore further into molecular mechanisms, we evaluated the effect of SUMO-1 knockdown on the activation of Rac1/PAK1, a critical signaling pathway that controls cell motility. Our results indicated that SUMO-1-mediated SUMOylation controlled Rac1 activation and modulated downstream PAK1 activity. Inhibition of Rac1 or PAK1 also decreased migration and invasion of RA FLSs. Our findings suggest that SUMO-1 suppression could be protective against joint destruction in RA by inhibiting aggressive behavior of RA FLSs.
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影响因子：
3.1
作者：
S. Lefèvre;F. Meier;E. Neumann;U. Muller-Ladner
通讯作者：
S. Lefèvre;F. Meier;E. Neumann;U. Muller-Ladner
影响因子：
10.5
作者：
Yue X;Zhang C;Zhao Y;Liu J;Lin AW;Tan VM;Drake JM;Liu L;Boateng MN;Li J;Feng Z;Hu W
通讯作者：
Hu W
影响因子：
64.8
作者：
Bertolotto, Corine;Lesueur, Fabienne;Bressac-de Paillerets, Brigitte
通讯作者：
Bressac-de Paillerets, Brigitte
DOI：
10.1158/1078-0432.ccr-08-0618
发表时间：
2008-08-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Brantley EC;Nabors LB;Gillespie GY;Choi YH;Palmer CA;Harrison K;Roarty K;Benveniste EN
通讯作者：
Benveniste EN
影响因子：
--
作者：
C. García‐Porrúa;M. González-Gay;M. Vázquez-Caruncho;L. López-Lázaro;M. Lueiro;M. Fernandez;J. Alvarez‐Ferreira;R. Pujol
通讯作者：
C. García‐Porrúa;M. González-Gay;M. Vázquez-Caruncho;L. López-Lázaro;M. Lueiro;M. Fernandez;J. Alvarez‐Ferreira;R. Pujol