Research Papers:

CD147 regulates cancer migration via direct interaction with Annexin A2 and DOCK3-β-catenin-WAVE2 signaling

Hong-Yong Cui, Shi-Jie Wang, Ji-Yu Miao, Zhi-Guang Fu, Fei Feng, Jiao Wu, Xiang-Min Yang, Zhi-Nan Chen and Jian-Li Jiang _

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Oncotarget. 2016; 7:5613-5629. https://doi.org/10.18632/oncotarget.6723

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Hong-Yong Cui1,*, Shi-Jie Wang1,*, Ji-Yu Miao1,*, Zhi-Guang Fu1,*, Fei Feng1, Jiao Wu1, Xiang-Min Yang1, Zhi-Nan Chen1 and Jian-Li Jiang1

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

* These authors contributed equally to the work

Correspondence to:

Jian-Li Jiang, email:

Zhi-Nan Chen, email:

Keywords: CD147, Annexin A2, DOCK3, WAVE2, cell movement

Received: June 24, 2015 Accepted: December 12, 2015 Published: December 22, 2015


The acquisition of inappropriate migratory feature is crucial for tumor metastasis. It has been suggested that CD147 and Annexin A2 are involved in regulating tumor cell movement, while the regulatory mechanisms are far from clear. In this study, we demonstrated that CD147 physically interacted with the N-terminal domain of Annexin A2 and decreased Annexin A2 phosphorylation on tyrosine 23. In vitro kinase assay showed that the I domain of CD147 was indispensable for CD147-mediated downregulation of Annexin A2 phosphorylation by Src. Furthermore, we determined that p-Annexin A2 promoted the expression of dedicator of cytokinesis 3 (DOCK3) and DOCK3 blocked β-catenin nuclear translocation, resulting in inhibition of β-catenin signaling. In addition, DOCK3 inhibited lamellipodium dynamics and tumor cell movement. Also, we found that β-catenin signaling increased WAVE2 expression. Therefore, DOCK3 was characterized as a negative regulator of WAVE2 expression via inhibiting β-catenin signaling. Our study provides the first evidence that CD147 promotes tumor cell movement and metastasis via direct interaction with Annexin A2 and DOCK3-β-catenin-WAVE2 signaling axis.

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