Oncotarget

Research Papers:

CD147 promotes Src-dependent activation of Rac1 signaling through STAT3/DOCK8 during the motility of hepatocellular carcinoma cells

Shi-Jie Wang, Hong-Yong Cui, Yan-Mei Liu, Pu Zhao, Yang Zhang, Zhi-Guang Fu, Zhi-Nan Chen and Jian-Li Jiang _

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Oncotarget. 2015; 6:243-257. https://doi.org/10.18632/oncotarget.2801

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Abstract

Shi-Jie Wang1,*, Hong-Yong Cui1,*, Yan-Mei Liu1,*, Pu Zhao2, Yang Zhang1, Zhi-Guang Fu1, Zhi-Nan Chen1 and Jian-Li Jiang1

1 Cell Engineering Research Center & Department of Cell Biology, State Key Laboratory of Cancer Biology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi’an, China

2 College of Life and Health Sciences, Northeastern University, Shenyang, China

* These authors contributed equally to this work

Correspondence:

Jian-Li Jiang, email:

Zhi-Nan Chen, email:

Keywords: CD147; Src; Rac1; DOCK8; STAT3

Received: August 28, 2014 Accepted: November 15, 2014 Published: November 16, 2014

Abstract

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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