CD147 promotes Src-dependent activation of Rac1 signaling through STAT3/DOCK8 during the motility of hepatocellular carcinoma cells.
CD147 promotes Src-dependent activation of Rac1 signaling through STAT3/DOCK8 during the motility of hepatocellular carcinoma cells.
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CD147 在肝细胞癌细胞运动过程中通过 STAT3/DOCK8 促进 Rac1 信号的 Src 依赖性激活。
DOI：
10.18632/oncotarget.2801
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发表时间：
2015-01-01
期刊：
影响因子：
--
通讯作者：
Jiang JL
中科院分区：
文献类型：
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作者：
Wang SJ;Cui HY;Liu YM;Zhao P;Zhang Y;Fu ZG;Chen ZN;Jiang JL
转移被认为是肿瘤发展的一个动态过程，与异常迁移和侵袭有关。肿瘤细胞可作为单个细胞以两种可转换的模式运动：间充质型和变形虫型。先前，我们报道了CD147和Annexin II之间的相互作用可以抑制肝细胞癌（HCC）细胞中的阿米巴运动。然而，CD147参与间质运动的机制尚不清楚。值得注意的是，我们的研究结果显示，CD147的过表达导致HCC细胞的间质型运动。通过共聚焦显微镜和Rac1活性测定，有证据表明CD147诱导的间充质型细胞运动是Src依赖的。Src的磷酸化（pY416-Src）可被CD147上调，而这种调节是由focal adhesion kinase （FAK）介导的。接下来，我们确定DOCK8是驱动间质型运动的关键分子Rac1的GEF。我们还发现Src促进STAT3磷酸化，STAT3促进DOCK8转录，从而增强DOCK8表达和Rac1激活。本研究提供了CD147调节HCC细胞间质型运动的新机制。
Metastasis is considered a dynamic process in tumor development that is related to abnormal migration and invasion. Tumor cells can move as individual cells in two interconvertible modes: mesenchymal-type and amoeboid. Previously, we reported that the interaction between CD147 and Annexin II can inhibit the amoeboid movement in hepatocellular carcinoma (HCC) cells. However, the mechanism of CD147 involved in mesenchymal movement is still unclear. Notably, our results show overexpression of CD147 led to mesenchymal-type movement in HCC cells. Evidence indicated that the mesenchymal-type cell movement induced by CD147 was Src dependent, as observed by confocal microscopy and Rac1 activity assay. The phosphorylation of Src (pY416-Src) can be up-regulated by CD147, and this regulation is mediated by focal adhesion kinase (FAK). Next, we identified DOCK8 as a GEF for Rac1, a key molecule driving mesenchymal-type movement. We also found that Src promotes STAT3 phosphorylation and STAT3 facilitates DOCK8 transcription, thus enhancing DOCK8 expression and Rac1 activation. This study provides a novel mechanism of CD147 regulating mesenchymal-type movement in HCC cells.
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影响因子：
5.4
作者：
Lambe, Teresa;Crawford, Greg;Johnson, Andy L.;Crockford, Tanya L.;Bouriez-Jones, Tiphaine;Smyth, Aisling M.;Pham, Trung H. M.;Zhang, Qian;Freeman, Alexandra F.;Cyster, Jason G.;Su, Helen C.;Cornall, Richard J.
通讯作者：
Cornall, Richard J.
DOI：
10.1186/1478-811x-8-23
发表时间：
2010-09-07
期刊：
Cell communication and signaling : CCS
影响因子：
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作者：
Parri M;Chiarugi P
通讯作者：
Chiarugi P
影响因子：
6.4
作者：
Li, Yu;Xu, Jing;Chen, Zhi-Nan
通讯作者：
Chen, Zhi-Nan
影响因子：
6.4
作者：
Dai, Lu;Bratoeva, Momka;Toole, Bryan P.;Qin, Zhiqiang;Parsons, Chris
通讯作者：
Parsons, Chris
影响因子：
30.5
作者：
通讯作者：
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