Effects of differential distributed-JUP on the malignancy of gastric cancer.
Effects of differential distributed-JUP on the malignancy of gastric cancer.
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差异分布JUP对胃癌恶性程度的影响
DOI：
10.1016/j.jare.2020.06.026
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发表时间：
2021-03
影响因子：
10.7
通讯作者：
Hou Y
中科院分区：
文献类型：
--
作者：
Chen Y;Yang L;Qin Y;Liu S;Qiao Y;Wan X;Zeng H;Tang X;Liu M;Hou Y
JUP是β-catenin的同源物，是一种参与粘附连接和桥粒组成的细胞-细胞连接蛋白。JUP在不同的恶性肿瘤中可能有不同的作用，依赖于它作为转录因子与β-catenin的能力或协作。在这项研究中，我们揭示了JUP的功能与其在GC从上皮样、低度恶性GC到晚期EMT表型GC的发展过程中的细胞定位有关。细胞膜和/或细胞质JUP的逐渐丢失与胃癌的恶性程度和预后不良密切相关。上皮样GC细胞中JUP的敲低导致EMT并促进GC细胞迁移和侵袭。野生JUP在恶性GC细胞中的异位表达导致减弱的恶性表型，例如降低的细胞侵袭潜力。在机制上，细胞膜和/或细胞质JUP的丢失消除了JUP对细胞膜上EGFR的抑制，并导致p-AKT水平和AKT/GSK 3 β/β-catenin信号活性增加。此外，核JUP与核β-catenin和TCF 4相互作用，协同促进TCF 4转录及其下游靶点MMP 7表达，为胃癌细胞侵袭提供能量。
JUP, a homologue of β-catenin, is a cell-cell junction protein involved in adhesion junction and desmosome composition. JUP may have a controversial role in different malignancies dependence of its competence with or collaboration with β-catenin as a transcription factor. In this study, we reveal that the function of JUP is related to its cellular location in GC development process from epithelium-like, low malignant GC to advanced EMT-phenotypic GC. Gradual loss of membrane and/or cytoplasm JUP is closely correlated with GC malignancy and poor prognostics. Knockdown of JUP in epithelium-like GC cells causes EMT and promotes GC cell migration and invasion. Ectopic expression of wild JUP in malignant GC cells leads to an attenuated malignant phenotype such as reduced cell invasive potential. In mechanism, loss of membrane and/or cytoplasm JUP abolishes the restrain of JUP to EGFR at cell membrane and results in increased p-AKT levels and AKT/GSK3β/β-catenin signaling activity. In addition, nuclear JUP interacts with nuclear β-catenin and TCF4 and plays a synergistic role with β-catenin in promoting TCF4 transcription and its downstream target MMP7 expression to fuel GC cell invasion.
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影响因子：
3.7
作者：
Mahendram S;Kelly KF;Paez-Parent S;Mahmood S;Polena E;Cooney AJ;Doble BW
通讯作者：
Doble BW
影响因子：
6.6
作者：
Wang, Liyang;Hou, Yixuan;Sung, Yan;Zhao, Liuyang;Tang, Xi;Hu, Ping;Yang, Jiajia;Zeng, Zongyue;Yang, Guanglun;Cui, Xiaojiang;Liu, Manran
通讯作者：
Liu, Manran
影响因子：
11.4
作者：
Morgan, R. G.;Pearn, L.;Liddiard, K.;Pumford, S. L.;Burnett, A. K.;Tonks, A.;Darley, R. L.
通讯作者：
Darley, R. L.
影响因子：
--
作者：
Aktary Z;Alaee M;Pasdar M
通讯作者：
Pasdar M
影响因子：
4
作者：
Aktary, Zackie;Kulak, Stephen;Pasdar, Manijeh
通讯作者：
Pasdar, Manijeh