MICAL2 Facilitates Gastric Cancer Cell Migration via MRTF-A-Mediated CDC42 Activation.
MICAL2 Facilitates Gastric Cancer Cell Migration via MRTF-A-Mediated CDC42 Activation.
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MICAL2 通过 MRTF-A 介导的 CDC42 激活促进胃癌细胞迁移
DOI：
10.3389/fmolb.2021.568868
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发表时间：
2021
影响因子：
5
通讯作者：
Du J
中科院分区：
文献类型：
--
作者：
Wang Y;Min P;Qi C;Zhao S;Yu M;Zhang Y;Du J
目的和假设：细胞迁移是由肌动蛋白细胞骨架的重组驱动的。尽管已知MICAL 2介导肌动蛋白丝的氧化以调节F-肌动蛋白动力学，但相对较少的研究调查了MICAL 2在癌细胞迁移期间的潜在作用。方法：采用创伤愈合法和transwell法检测胃癌细胞的迁移能力。利用基因过表达和敲低策略分析MICAL 2表达与MRTF-A核定位之间的关系。DCFH-DA染色检测细胞内活性氧（ROS）的产生。使用qPCR和免疫印迹分析测量MMP 9的mRNA和蛋白水平。使用下拉测定法评估CDC 42和RhoA的活性。结果：MICAL 2的缺失显著减少胃癌细胞的迁移。在机制上，MICAL 2的沉默抑制了MRTF-A在EGF和血清刺激下的核转位，而MRTF-A的含量保持不变。进一步的分析表明，MICAL 2的沉默降低了CDC 42的活化以及MMP 9的mRNA和蛋白水平。MICAL 2的异位表达增加了MRTF-A在细胞核中的表达，并促进了CDC 42、MMP 9表达的激活和胃癌细胞的迁移。此外，沉默MRTF-A抑制了由MICAL 2过表达诱导的CDC 42活化。此外，MICAL 2诱导的ROS产生有助于MICAL 2对MRTF-A核转位的影响。结论：总之，这些结果提供了证据表明MICAL 2通过正向调节MRTF-A的核转位以及随后的CDC 42活化和MMP 9表达促进胃癌细胞迁移。
Aims and Hypothesis: Cell migration is driven by the reorganization of the actin cytoskeleton. Although MICAL2 is known to mediate the oxidation of actin filaments to regulate F-actin dynamics, relatively few studies have investigated the potential role of MICAL2 during cancer cell migration. Methods: The migratory ability of gastric cancer cells was measured by wound healing and transwell assays. The relationship between MICAL2 expression and MRTF-A nuclear localization was analyzed using gene overexpression and knockdown strategies. The production of reactive oxygen species (ROS) was evaluated by DCFH-DA staining. mRNA and protein levels of MMP9 were measured using qPCR and immunoblotting analysis. The activities of CDC42 and RhoA were assessed using pulldown assays. Results: Depletion of MICAL2 markedly reduced gastric cancer cell migration. Mechanistically, silencing of MICAL2 inhibited the nuclear translocation of MRTF-A in response to EGF and serum stimulation, whereas the contents of MRTF-A remained unchanged. Further analysis showed that silencing of MICAL2 decreased the activation of CDC42 as well as mRNA and protein levels of MMP9. Ectopic expression of MICAL2 augmented MRTF-A levels in the nucleus, and promoted the activation of CDC42, MMP9 expression, and gastric cancer cell migration. Moreover, silencing of MRTF-A inhibited the CDC42 activation induced by overexpression of MICAL2. In addition, MICAL2-induced ROS generation contributed to the effect exerted by MICAL2 on MRTF-A nuclear translocation. Conclusion: Together, these results provide evidence that MICAL2 facilitates gastric cancer cell migration via positive regulation of nuclear translocation of MRTF-A and subsequent CDC42 activation and MMP9 expression.
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影响因子：
--
作者：
Mariotti S;Barravecchia I;Vindigni C;Pucci A;Balsamo M;Libro R;Senchenko V;Dmitriev A;Jacchetti E;Cecchini M;Roviello F;Lai M;Broccoli V;Andreazzoli M;Mazzanti CM;Angeloni D
通讯作者：
Angeloni D
Scinderin促进胃癌细胞的侵袭和转移并预测患者的预后
影响因子：
9.7
作者：
Liu JJ;Liu JY;Chen J;Wu YX;Yan P;Ji CD;Wang YX;Xiang DF;Zhang X;Zhang P;Cui YH;Wang JM;Bian XW;Qian F
通讯作者：
Qian F
影响因子：
5.7
作者：
Guo Y;Kenney SR;Muller CY;Adams S;Rutledge T;Romero E;Murray-Krezan C;Prekeris R;Sklar LA;Hudson LG;Wandinger-Ness A
通讯作者：
Wandinger-Ness A
影响因子：
64.5
作者：
Lundquist MR;Storaska AJ;Liu TC;Larsen SD;Evans T;Neubig RR;Jaffrey SR
通讯作者：
Jaffrey SR
影响因子：
3.4
作者：
Du, Dong-Shu;Yang, Xiao-Zhong;Tang, Xiao-Jun
通讯作者：
Tang, Xiao-Jun