Leucine-rich repeat-containing G-protein-coupled receptor 5 is associated with invasion, metastasis, and could be a potential therapeutic target in human gastric cancer.
Leucine-rich repeat-containing G-protein-coupled receptor 5 is associated with invasion, metastasis, and could be a potential therapeutic target in human gastric cancer.
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富含亮氨酸重复序列的 G 蛋白偶联受体 5 与侵袭、转移相关，可能是人类胃癌的潜在治疗靶点
DOI：
10.1038/bjc.2014.112
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发表时间：
2014-04-15
影响因子：
8.8
通讯作者：
Chen, L.
中科院分区：
文献类型：
--
作者：
Xi, H. Q.;Cai, A. Z.;Wu, X. S.;Cui, J. X.;Shen, W. S.;Bian, S. B.;Wang, N.;Li, J. Y.;Lu, C. R.;Song, Z.;Wei, B.;Chen, L.
富含亮氨酸重复序列的g蛋白偶联受体5 （Lgr5）是一种新的肠道干细胞标志物，在多种肿瘤中过表达。在本研究中，我们探讨了Lgr5在胃癌中的表达，并分析了其在胃癌侵袭、转移和预后中的作用。采用免疫组织化学、免疫印迹和定量逆转录聚合酶链反应相结合的方法检测Lgr5和基质金属蛋白酶2 (MMP2) mRNA和蛋白的表达水平。设计合成Lgr5小干扰RNA，转染AGS细胞。通过transwell侵袭室实验和伤口愈合实验检测Lgr5 siRNA对细胞侵袭的影响。富亮氨酸重复-含g蛋白偶联受体5在胃癌中的表达明显高于正常粘膜。富亮氨酸重复-含g蛋白偶联受体5表达与浸润深度、淋巴结转移、转移距离、MMP2表达水平呈正相关。多因素分析显示Lgr5对生存率有独立影响，且与MMP2呈正相关。富含亮氨酸重复序列的g蛋白偶联受体5 sirna抑制Lgr5 mRNA和蛋白表达。Transwell实验表明，这些sirna显著减少了细胞通过聚碳酸酯膜的迁移，伤口愈合实验也表明sirna减少了细胞的迁移。与对照组相比，Lgr5的抑制导致MMP2和β-catenin水平显著降低。富亮氨酸重复序列-含g蛋白偶联受体5与侵袭转移相关。富含亮氨酸的含重复g蛋白偶联受体5抑制可能是一种新的治疗方法。
Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5), which is identified as a novel intestinal stem cell marker, is overexpressed in various tumours. In this study, we explore Lgr5 expression in gastric carcinoma and analyse its role in invasion, metastasis, and prognosis in carcinoma. A combination of immunohistochemistry, western blotting, and quantitative reverse transcription–polymerase chain reaction were used to detect mRNA and protein expression levels of Lgr5 and matrix metalloproteinase 2 (MMP2). Small interfering RNA against Lgr5 was designed, synthesised, and transfected into AGS cells. The effects of Lgr5 siRNA on cell invasion were detected by transwell invasion chamber assay and wound healing assay. Leucine-rich repeat-containing G-protein-coupled receptor 5 expression was significantly higher in gastric carcinomas than in normal mucosa. Leucine-rich repeat-containing G-protein-coupled receptor 5 expression positively correlated with the depth of invasion, lymph node metastasis, distance of metastasis, and MMP2 expression levels. Multivariate analysis showed that Lgr5 had an independent effect on survival, and that it positively correlated with MMP2. Leucine-rich repeat-containing G-protein-coupled receptor 5 siRNAs inhibited Lgr5 mRNA and protein expression. Transwell assays indicated that these siRNAs resulted in significantly fewer cells migrating through the polycarbonate membrane, and wound healing assay also indicated that siRNAs decreased the migration of cells. Inhibition of Lgr5 resulted in a significant decrease in MMP2 and β-catenin levels compared with those in controls. Leucine-rich repeat-containing G-protein-coupled receptor 5 was correlated with invasion and metastasis. Leucine-rich repeat-containing G-protein-coupled receptor 5 inhibition could serve as a novel therapeutic approach.
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影响因子：
2
作者：
Alakus, H.;Grass, G.;Moenig, S. P.
通讯作者：
Moenig, S. P.
影响因子：
8.8
作者：
Sier CF;Kubben FJ;Ganesh S;Heerding MM;Griffioen G;Hanemaaijer R;van Krieken JH;Lamers CB;Verspaget HW
通讯作者：
Verspaget HW
影响因子：
0.4
作者：
Anbiaee R;Mojir Sheibani K;Torbati P;Jaam H
通讯作者：
Jaam H
DOI：
10.6004/jnccn.2010.0033
发表时间：
2010-04-01
影响因子：
13.4
作者：
Shah, Manish A.;Kelsen, David P.
通讯作者：
Kelsen, David P.
DOI：
10.5114/wo.2013.34618
发表时间：
2013
期刊：
Contemporary oncology (Poznan, Poland)
影响因子：
--
作者：
Guo Y;Yin J;Zha L;Wang Z
通讯作者：
Wang Z