PSMA1 mediates tumor progression and poor prognosis of gastric carcinoma by deubiquitinating and stabilizing TAZ.
PSMA1 mediates tumor progression and poor prognosis of gastric carcinoma by deubiquitinating and stabilizing TAZ.
复制标题
PSMA1通过去泛素化和稳定TAZ介导胃癌的肿瘤进展和不良预后
DOI：
10.1038/s41419-022-05417-0
复制
发表时间：
2022-11-23
影响因子：
9
通讯作者：
Shu, Xu
中科院分区：
文献类型：
--
作者：
Yang, Qinyu;Lu, Ying;Shangguan, Jianfang;Shu, Xu
肿瘤进展中的去泛素化酶家族在细胞内蛋白质降解中发挥重要作用。据报道，蛋白酶体 α 1 型亚基 (PSMA1) 在多种人类癌症中充当癌基因。本研究旨在揭示 PSMA1 在胃癌（GC）进展中的功能意义及其潜在机制。通过蛋白质印迹分析、实时PCR、免疫组织化学（IHC）和体外泛素化实验检测人GC样本和GC细胞系中PSMA1的表达，并建立异种移植小鼠模型。我们发现PSMA1在GC中上调并促进GC细胞的增殖、迁移和侵袭。在此，我们报道具有 PDZ 结合基序 (TAZ) 的转录共激活因子是 PSMA1 的下游基因。从机制上讲，PSMA1 通过 GC 中的去泛素化直接与 TAZ 相互作用并稳定 TAZ。此外，我们发现 TAZ 是 PSMA1 调节体外和体内致癌活性的重要介质。临床样本检查证实，PSMA1 介质升高，伴随着 TAZ 丰度增加，与人类 GC 进展相关。这些数据表明 PSMA1 通过使 TAZ 去泛素化来促进 GC 进展和增殖。 PSMA1 通过 PSMA1 介导的去泛素化酶活性促进 GC 进展和增殖，并为 GC 管理提供潜在的治疗靶点。
The deubiquitinating enzyme family in tumor progression play important role in intracellular protein degradation. The proteasome subunit alpha type 1 (PSMA1) has been reported to act as an oncogene in several human cancers. The present study aimed to reveal the functional significance of PSMA1 in gastric cancer (GC) progression and the underlying mechanisms. The expression of PSMA1 in human GC samples and GC cell lines was examined by western blot analysis, real-time PCR, immunohistochemistry (IHC), and in vitro ubiquitination assays and established a xenograft mouse model. We found that PSMA1 was upregulated in GC and promoted proliferation, migration and invasion in GC cells. Herein, we report transcriptional co-activator with PDZ-binding motif (TAZ) was a downstream gene of PSMA1. Mechanistically, PSMA1 directly interacted with and stabilized TAZ via deubiquitination in GC. Furthermore, we found that TAZ was the essential mediator of PSMA1-modulated oncogenic activity in vitro and in vivo. Examination of clinical samples confirmed that elevated mediators of PSMA1, concomitant with increased TAZ abundance, correlate with human GC progression. These data suggested that PSMA1 promotes GC progression and proliferation by deubiquitinating TAZ. PSMA1 promotes GC progression and proliferation regarding PSMA1-mediated deubiquitinating enzyme activity and suggest potential therapeutic targets for GC management.
登录
查看更多内容
Hippo信号效应子WWTR1是胃贲门腺癌的转移生物标志物
影响因子：
5.8
作者：
Wei, Jing;Wang, Lincui;Lin, Qiong
通讯作者：
Lin, Qiong
影响因子：
5.2
作者：
Mussell A;Shen H;Chen Y;Mastri M;Eng KH;Bshara W;Frangou C;Zhang J
通讯作者：
Zhang J
影响因子：
3.9
作者：
Goldberg, A. L.
通讯作者：
Goldberg, A. L.
CDK4/6 依赖性 DUB3 激活通过 SNAIL1 调节癌症转移。
影响因子：
16.6
作者：
Liu T;Yu J;Deng M;Yin Y;Zhang H;Luo K;Qin B;Li Y;Wu C;Ren T;Han Y;Yin P;Kim J;Lee S;Lin J;Zhang L;Zhang J;Nowsheen S;Wang L;Boughey J;Goetz MP;Yuan J;Lou Z
通讯作者：
Lou Z
影响因子：
20.3
作者：
Fang, Jing;Rhyasen, Garrett;Starczynowski, Daniel T.
通讯作者：
Starczynowski, Daniel T.