Definition of a direct extracellular interaction between Met and E-cadherin

Authors

  • Galina Reshetnikova,

    Corresponding author
    1. Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA
    2. Institute of Cytology of Russian Academy of Sciences, St. Petersburg, Russian Federation
      Corresponding author. Institute of Cytology of Russian Academy of Sciences, Tikhoretsky Avenue 4, St. Petersburg 194064, Russia. Tel.: +7 812 297 4596; fax: +7 812 297 0341. greshet@mail.cytspb.rssi.ru
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  • Sergei Troyanovsky,

    1. Department of Cell Biology, Washington University School of Medicine, St. Louis, MO, USA
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  • David L. Rimm

    1. Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA
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Corresponding author. Institute of Cytology of Russian Academy of Sciences, Tikhoretsky Avenue 4, St. Petersburg 194064, Russia. Tel.: +7 812 297 4596; fax: +7 812 297 0341. greshet@mail.cytspb.rssi.ru

Abstract

High levels of the Met tyrosine kinase receptor expression are associated with metastatic disease. Met activation by hepatocyte growth factor (HGF) is associated with decreased E-cadherin-dependent cell—cell contacts. The molecular mechanism underlying this process remains unclear. To better understand the relationship between E-cadherin and Met, we assessed Met localization in cells which form mature E-cadherin-dependent adhesion HT-29 and cells which have lost E-cadherin expression BT-549. Met colocalized with E-cadherin at the site of cell—cell adhesion in HT-29 cells, but Met was distributed in an intracellular compartment in BT-549 cells. Forced expression of E-cadherin in BT-549 cells recruited Met to the membrane. Cross-linking studies suggested that Met and E-cadherin interact in the extracellular domain in HT-29 cells. This is the first evidence of a physical interaction between Met and E-cadherin. We suggest that this receptor/cadherin pairing may be a mechanism for cellular presentation of receptors in a manner that localizes them optimally for interaction with ligand.

Ancillary