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Deficiency in VHR/DUSP3, a suppressor of focal adhesion kinase, reveals its role in regulating cell adhesion and migration

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Abstract

Vaccinia H1-related phosphatase (VHR/DUSP3) is a member of the dual-specificity phosphatase family. Deregulation of VHR is observed in various malignant diseases. We identified focal adhesion kinase (FAK) as a VHR-interacting molecule. Over-expression of VHR decreased tyrosine phosphorylation of FAK and decreasing VHR promoted FAK tyrosine phosphorylation. In vitro assays proved that recombinant VHR directly dephosphorylated FAK and paxillin. VHR-knockout mice did not have obvious abnormality; however, VHR-knockout cells showed decreased expression of integrins and FAK but stronger FAK and paxillin phosphorylation upon attachment to fibronectin. Additionally, VHR-knockout fibroblast and lung epithelial cells had elevated ligand-induced epidermal growth factor receptor (EGFR) phosphorylation. Inducible expression of VHR suppressed directional cell migration, and VHR deficiency resulted in a higher cell migratory ability. VHR-knockout cells have stronger FAK phosphorylation in cell adhesions, long-lasting trailing ends and slower turnover of focal adhesions. These collective data indicate that VHR is a FAK phosphatase and participates in regulating the formation and disassembly of focal adhesions.

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Acknowledgements

We thank National Health Research Institutes Transgenic Animal Core for assistance in the mouse blastocyst injection and Optical Biology Core for the assistance in confocal microscopy and time-lapsed photography analyses. This work was supported by grants from National Health Research Institutes, Taiwan (MG-102-PP-03 and MG-103-PP-03 to Y-R Chen; 105-IMPP01 and 105-IMSP01 to T-H Tan), and grants from Ministry of Science and Technology, Taiwan (102-2628-B-400-003 to Y-R Chen and 105-2314-B-400-027 to T-H Tan).

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Authors and Affiliations

  1. Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan, Taiwan

    Y-R Chen, H-C Chou, C-H Yang, H-Y Chen, Y-W Liu, T-Y Lin & C-L Yeh

  2. Department of Life Science, Tunghai University, Taichung, Taiwan

    H-Y Chen & W-T Chao

  3. Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan

    H-H Tsou

  4. Graduate Institute of Biostatistics, College of Public Health, China Medical University, Taichung, Taiwan

    H-H Tsou

  5. Immunology Research Center, National Health Research Institutes, Zhunan, Taiwan

    H-C Chuang & T-H Tan

  6. Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA

    T-H Tan

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Chen, YR., Chou, HC., Yang, CH. et al. Deficiency in VHR/DUSP3, a suppressor of focal adhesion kinase, reveals its role in regulating cell adhesion and migration. Oncogene 36, 6509–6517 (2017). https://doi.org/10.1038/onc.2017.255

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