DUSP1 inhibits cell proliferation, metastasis and invasion and angiogenesis in gallbladder cancer

被引：37

作者：

Shen, Jiliang ^{[1
]}

Zhou, Senjun ^{[1
]}

Shi, Liang ^{[1
]}

Liu, Xiaolong ^{[1
]}

Lin, Hui ^{[1
]}

Yu, Hong ^{[1
]}

Liang, Xiao ^{[1
]}

Tang, Jiacheng ^{[1
]}

Yu, Tunan ^{[1
]}

Cai, Xiujun ^{[1
]}

机构：

[1] Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Gen Surg, Hangzhou 310016, Zhejiang, Peoples R China

来源：

ONCOTARGET | 2017年 / 8卷 / 07期

关键词：

DUSP1; gallbladder cancer; metastasis; angiogenesis; MMP2; ENDOTHELIAL GROWTH-FACTOR; TUMOR ANGIOGENESIS; COLORECTAL-CANCER; MATRIX METALLOPROTEINASE-2; HEPATOCELLULAR-CARCINOMA; GASTRIC-CANCER; RECTAL-CANCER; LUNG-CANCER; EXPRESSION; PROMOTES;

D O I：

10.18632/oncotarget.14815

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

DUSP1/MKP1 is a dual-specific phosphatase that regulates MAPK activity and is known to play a key role in tumor biology. Its function in gallbladder cancer (GBC) remains largely unknown, however. By exploring its activities in two GBC cell lines (SGC996 and GBC-SD), DUSP1 was found to inhibit GBC cell proliferation, migration and invasion. Moreover, DUSP1 inhibited GBC growth and metastasis in nude mice subcutaneously xenografted with SGC996 cells. The tumor suppression appeared to be mediated via the DUSP1-pERK/MAPK-MMP2 signal pathway. Angiogenesis was associated with the tumor metastasis in the mouse model and was impaired by DUSP1, which suppressed VEGF expression. These results suggest that DUSP1 suppresses GBC growth and metastasis by targeting the DUSP1-pERK-MMP2/VEGF axis. Identification of the DUSP1-pERK-MMP2/VEGF signals may provide new biomarkers and/or therapeutic targets to better suppress GBC metastasis in the future.

引用

页码：12133 / 12144

页数：12

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