Inhibition of chromosomal region maintenance 1 suppresses the migration and invasion of glioma cells via inactivation of the STAT3/MMP2 signaling pathway
Inhibition of chromosomal region maintenance 1 suppresses the migration and invasion of glioma cells via inactivation of the STAT3/MMP2 signaling pathway
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抑制染色体区域维护1通过灭活STAT3/MMP2信号通路抑制胶质瘤细胞的迁移和侵袭
DOI：
10.4196/kjpp.2020.24.3.193
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发表时间：
2020-05
影响因子：
2
通讯作者：
Liu Xuejiao
中科院分区：
文献类型：
--
作者：
Shan Qianqian;Li Shengsheng;Cao Qiyu;Yue Chenglong;Niu Mingshan;Chen Xiangyu;Shi Lin;Li Huan;Gao Shangfeng;Liang Jun;Yu Rutong;Liu Xuejiao
染色体区域维持1（CRM1）与胶质瘤的不良预后相关。我们以前报道过CRM1抑制抑制胶质瘤细胞增殖在体外和体内。在这项研究中，我们研究了CRM1在胶质瘤细胞迁移和侵袭中的作用。用新型CRM1选择性可逆抑制剂S109处理人胶质瘤U87和U251细胞。通过伤口愈合和transwell侵袭试验评估细胞迁移和侵袭。结果表明，S109对U87和U251细胞的迁移和侵袭有明显的抑制作用。然而，CRM1中Cys528突变取消了S109在胶质瘤细胞中的抑制活性。此外，我们发现S109处理降低MMP 2的表达水平和活性，降低磷酸化STAT3的水平，但不降低总STAT3的水平。因此，S109抑制细胞迁移和侵袭可能与下调MMP 2的活性和表达，以及STAT3信号通路的失活有关。这些结果支持了我们先前的结论，即抑制CRM1是治疗胶质瘤的有吸引力的策略。
Chromosomal region maintenance 1 (CRM1) is associated with an adverse prognosis in glioma. We previously reported that CRM1 inhibition suppressed glioma cell proliferation both in vitro and in vivo. In this study, we investigated the role of CRM1 in the migration and invasion of glioma cells. S109, a novel reversible selective inhibitor of CRM1, was used to treat Human glioma U87 and U251 cells. Cell migration and invasion were evaluated by wound-healing and transwell invasion assays. The results showed that S109 significantly inhibited the migration and invasion of U87 and U251 cells. However, mutation of Cys528 in CRM1 abolished the inhibitory activity of S109 in glioma cells. Furthermore, we found that S109 treatment decreased the expression level and activity of MMP2 and reduced the level of phosphorylated STAT3 but not total STAT3. Therefore, the inhibition of migration and invasion induced by S109 may be associated with the downregulation of MMP2 activity and expression, and inactivation of the STAT3 signaling pathway. These results support our previous conclusion that inhibition of CRM1 is an attractive strategy for the treatment of glioma.
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影响因子：
4.6
作者：
Panth KM;van den Beucken T;Biemans R;Lieuwes NG;Weber M;Losen M;Yaromina A;Dubois LJ;Lambin P
通讯作者：
Lambin P
影响因子：
2.2
作者：
Yang Q;Wang WW;Ma P;Ma ZX;Hao M;Adelusi TI;Lei-Du;Yin XX;Lu Q
通讯作者：
Lu Q
DOI：
10.1172/jci15372
发表时间：
2003-02
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
S. Bhattacharya;C. Schindler
通讯作者：
S. Bhattacharya;C. Schindler
影响因子：
3.9
作者：
Senft, Christian;Priester, Maike;Weissenberger, Jakob
通讯作者：
Weissenberger, Jakob
影响因子：
2.8
作者：
F. Zhou;Ercheng Chen;D. You;Yipeng Song;Zhenni Sun;L. Yue
通讯作者：
F. Zhou;Ercheng Chen;D. You;Yipeng Song;Zhenni Sun;L. Yue