High G2 and S-phase expressed 1 expression promotes acral melanoma progression and correlates with poor clinical prognosis.
High G2 and S-phase expressed 1 expression promotes acral melanoma progression and correlates with poor clinical prognosis.
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高 G2 和 S 期表达 1 表达促进肢端黑色素瘤进展并与不良临床预后相关
DOI：
10.1111/cas.13607
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发表时间：
2018-06
期刊：
影响因子：
5.7
通讯作者：
Guo J
中科院分区：
文献类型：
--
作者：
Xu T;Ma M;Chi Z;Si L;Sheng X;Cui C;Dai J;Yu S;Yan J;Yu H;Wu X;Tang H;Yu J;Kong Y;Guo J
G2和S期表达1（GTSE 1）调节人类癌症的细胞周期进程。然而，其在肢端黑色素瘤（AM）中的意义和作用机制仍不清楚。在本研究中，我们发现GTSE 1表达在晚期/转移性AM组织和转移性细胞系中上调，并与AM患者的高分期（P = .028）和低无病生存率（DFS）相关（P = .003）。考克斯回归分析证实GTSE 1表达是AM患者DFS的独立预后因素（P = .004）。GTSE 1的异位表达增强了原代AM细胞的增殖、侵袭和迁移。GTSE 1功能丧失在体外和体内减弱了转移性AM细胞增殖和转移能力。我们还观察到，迁移和侵袭的抑制伴随着GTSE 1敲低介导的E-钙粘蛋白增加以及N-钙粘蛋白和Slug减少。我们进一步表明，整合素亚基α 2（ITGA 2）与GTSE 1相互作用，是GTSE 1的下游效应子。此外，ITGA 2水平与人AM组织中的GTSE 1表达呈正相关。异位ITGA 2表达挽救了siGTSE 1介导的迁移和侵袭抑制，从而恢复了上皮向间质转化（EMT）。总之，GTSE 1表达促进AM进展，并与AM患者的临床结局相关，可能代表一个有前途的治疗靶点来抑制AM进展。
G2 and S‐phase expressed 1 (GTSE1) regulates cell cycle progression in human cancers. However, its significance and mechanism of action in acral melanoma (AM) remain unknown. In the present study, we found that GTSE1 expression was upregulated in advanced stage/metastatic AM tissues and metastatic cell lines, and correlated with higher stage (P = .028) and poor disease‐free survival (DFS) in patients with AM (P = .003). Cox regression assays validated GTSE1 expression to be an independent prognostic factor of DFS for patients with AM (P = .004). Ectopic expression of GTSE1 enhanced primary AM cell proliferation, invasion, and migration. Loss‐of‐function in GTSE1 attenuated metastatic AM cell proliferation and metastatic ability in vitro and in vivo. We additionally observed that inhibition of migration and invasion occurred concomitantly with a GTSE1 knockdown‐mediated increase in E‐cadherin and decreases in N‐cadherin and Slug. We further showed that integrin subunit alpha 2 (ITGA2) interacts with GTSE1 and is a downstream effector of GTSE1. Further, ITGA2 levels were positively correlated with GTSE1 expression in human AM tissues. Ectopic ITGA2 expression rescued siGTSE1‐mediated inhibition of migration and invasion, thereby restoring epithelial‐to‐mesenchymal transition (EMT). In conclusion, GTSE1 expression promotes AM progression and correlates with clinical outcomes of patients with AM, and may represent a promising therapeutic target to suppress AM progression.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
DOI：
10.1158/1541-7786.mcr-11-0311
发表时间：
2011-11
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Augoff K;Das M;Bialkowska K;McCue B;Plow EF;Sossey-Alaoui K
通讯作者：
Sossey-Alaoui K
影响因子：
--
作者：
Bradford, Porcia T.;Goldstein, Alisa M.;McMaster, Mary L.;Tucker, Margaret A.
通讯作者：
Tucker, Margaret A.
影响因子：
11.2
作者：
Alonso, Soledad R.;Tracey, Lorraine;Rodriguez-Peralto, Jose L.
通讯作者：
Rodriguez-Peralto, Jose L.
中国黑色素瘤患者 KIT 畸变的大规模分析
影响因子：
11.5
作者：
Kong, Yan;Si, Lu;Guo, Jun
通讯作者：
Guo, Jun