Rho GTPase RhoJ is Associated with Gastric Cancer Progression and Metastasis.
Rho GTPase RhoJ is Associated with Gastric Cancer Progression and Metastasis.
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DOI：
10.7150/jca.15578
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发表时间：
2016
影响因子：
3.9
通讯作者：
Rha SY
中科院分区：
文献类型：
--
作者：
Kim C;Yang H;Park I;Chon HJ;Kim JH;Kwon WS;Lee WS;Kim TS;Rha SY
Rho GTP酶通过调节肿瘤细胞的迁移和侵袭在肿瘤进展中起关键作用。然而，Rho GTPases在胃癌（GC）中的作用仍有待研究。本研究旨在探讨Rho J的临床意义，Rho J是Rho家族的未知成员。分析了人GC细胞系和来自GC患者的手术标本中的RhoJ表达。此外，在体外功能获得性分析进行评估RhoJ过表达的GC细胞的恶性表型。RhoJ表达的程度在GC细胞系和GC患者中不同。YCC-9细胞表达最强，而YCC-10、-11和-16细胞表达较少。在70名胃癌患者中，48.6%的胃癌组织中有RhoJ表达，RhoJ高表达者弥漫型胃癌多见（73.5%对41.7%），处于更晚期阶段RhoJ基因在胃癌中的表达（III、IV期：85.3%对58.4%），并且具有更频繁的转移（47.1%对11.1%），表明RhoJ在胃癌进展和转移中具有潜在的作用。RhoJ高表达与胃癌手术切除后的总生存率和无复发生存率显著相关。最后，体外功能获得实验显示，与对照相比，RhoJ过表达的GC细胞的运动性增强41.3%，侵袭性增强60.4%，细胞增殖差异可忽略不计。总的来说，RhoJ高表达是胃癌生存结局的独立负性预后因素，并与细胞运动性和侵袭性增加相关。
Rho GTPases play a pivotal role in tumor progression by regulating tumor cell migration and invasion. However, the role of Rho GTPases in gastric cancer (GC) remains unexplored. This study aimed to investigate the clinical implications of RhoJ, which is an uncharted member of Rho family. RhoJ expression in human GC cell lines and surgical specimens from GC patients were analyzed. Moreover, in vitro gain-of-function analysis was performed to evaluate the malignant phenotypes of RhoJ-overexpressing GC cells. The extent of RhoJ expression varied among GC cell lines and GC patients. YCC-9 cell line displayed the strongest expression, while YCC-10, -11, and -16 showed scant expressions. Of the 70 GC patients, 34 (48.6%) had RhoJ expression in their GC tissue, and patients with high RhoJ expression had more diffuse type GC (73.5% vs. 41.7%), were at more advanced stages (stage III, IV: 85.3% vs. 58.4%), and had more frequent metastasis (47.1% vs. 11.1%), denoting that RhoJ has a potential role in GC progression and metastasis. High RhoJ expression significantly correlated with poor overall survival and recurrence-free survival after surgical resection of gastric cancer. Finally, In vitro gain-of-function experiments showed 41.3% enhanced motility and 60.4% enhanced invasiveness in RhoJ-overexpressing GC cells compared to control, with negligible difference in cell proliferation. Collectively, high RhoJ expression is an independent negative prognostic factor for the survival outcome of GC and correlated with the increased cell motility and invasiveness.