DUSP1 inhibits cell proliferation, metastasis and invasion and angiogenesis in gallbladder cancer.
DUSP1 inhibits cell proliferation, metastasis and invasion and angiogenesis in gallbladder cancer.
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DOI：
10.18632/oncotarget.14815
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发表时间：
2017-02-14
期刊：
影响因子：
--
通讯作者：
Cai X
中科院分区：
文献类型：
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作者：
Shen J;Zhou S;Shi L;Liu X;Lin H;Yu H;Xiaoliang;Tang J;Yu T;Cai X
DUSP 1/MKP 1是一种调节MAPK活性的双特异性磷酸酶，已知在肿瘤生物学中发挥关键作用。然而，它在胆囊癌（GBC）中的功能在很大程度上仍然未知。通过研究DUSP 1在两种GBC细胞系（SGC 996和GBC-SD）中的活性，发现DUSP 1抑制GBC细胞的增殖、迁移和侵袭。此外，DUSP 1抑制GBC的生长和转移与SGC 996细胞的裸鼠皮下移植瘤。肿瘤抑制似乎是通过DUSP 1-pERK/MAPK-MMP 2信号通路介导的。在小鼠模型中，血管生成与肿瘤转移相关，并受到抑制VEGF表达的DUSP 1的损害。这些结果表明DUSP 1通过靶向DUSP 1-pERK-MMP 2/VEGF轴抑制GBC生长和转移。DUSP 1-pERK-MMP 2/VEGF信号的识别可能会提供新的生物标志物和/或治疗靶点，以在未来更好地抑制GBC转移。
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.