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Characterization of Cell Membrane Extensions and Studying Their Roles in Cancer Cell Adhesion Dynamics
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CD147 regulates cancer migration via direct interaction with Annexin A2 and DOCK3-β-catenin-WAVE2 signaling

Hong-Yong Cui1, Shi-Jie Wang1, Ji-Yu Miao1

  • 1Cell 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.

Oncotarget
|December 31, 2015
PubMed

Insights

CD147 protein interaction with Annexin A2 promotes tumor cell movement and metastasis. This occurs through the DOCK3-beta-catenin-WAVE2 signaling pathway, highlighting a new therapeutic target for cancer spread.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Tumor metastasis involves acquiring migratory features.
  • CD147 and Annexin A2 are implicated in tumor cell movement, but mechanisms are unclear.

Purpose of the Study:

  • To elucidate the regulatory mechanisms of CD147 and Annexin A2 in tumor cell migration.
  • To investigate the role of CD147-Annexin A2 interaction in cancer metastasis.

Main Methods:

  • Co-immunoprecipitation to show physical interaction between CD147 and Annexin A2.
  • In vitro kinase assays to determine the effect of CD147 on Annexin A2 phosphorylation.
  • Western blotting and cell migration assays to analyze signaling pathways.

Main Results:

  • CD147 directly binds Annexin A2's N-terminal domain, reducing tyrosine 23 phosphorylation.
  • The I domain of CD147 is essential for Src-mediated downregulation of Annexin A2 phosphorylation.
  • Phosphorylated Annexin A2 upregulates DOCK3, which inhibits beta-catenin signaling and lamellipodium dynamics.
  • DOCK3 negatively regulates WAVE2 expression via the beta-catenin pathway, inhibiting tumor cell movement.

Conclusions:

  • CD147 promotes tumor cell migration and metastasis by interacting with Annexin A2.
  • The study identifies a novel CD147-Annexin A2-DOCK3-beta-catenin-WAVE2 signaling axis regulating tumor cell movement.
Keywords:
Annexin A2CD147DOCK3WAVE2cell movement

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