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ADAM15 suppresses cell motility by driving integrin alpha5beta1 cell surface expression via Erk inactivation

Qin Chen1, Ling-Hua Meng, Cai-Hua Zhu

  • 1Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.

The International Journal of Biochemistry & Cell Biology
|April 5, 2008
PubMed

Insights

This study reveals that ADAM15 (a disintegrin and metalloprotease domain 15) enhances alpha5 integrin expression by reducing Erk1/2 phosphorylation, impacting cell adhesion and migration. This novel mechanism reduces pulmonary metastasis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The ADAM15 protein contains an RGD motif, suggesting interaction with integrins.
  • The biological role of ADAM15 and its interaction with integrin alpha5beta1 remain unclear.

Purpose of the Study:

  • To investigate the effects of ADAM15 on alpha5beta1-mediated cell adhesion and migration.
  • To elucidate the underlying molecular mechanisms of ADAM15's function.

Main Methods:

  • Overexpression of human ADAM15 in CHO cells expressing integrin alpha5beta1.
  • Analysis of cell adhesion, migration, integrin expression, and Erk1/2 phosphorylation.
  • Utilized MEK inhibitor PD98059 and siRNA against Erk1/2.
  • Evaluated pulmonary metastasis using a B16F10 model.

Main Results:

  • ADAM15 overexpression enhanced cell adhesion and reduced migration on fibronectin.
  • Increased cell surface expression and clustering of alpha5 integrin, without affecting beta1.
  • ADAM15 decreased Erk1/2 phosphorylation; inhibiting Erk1/2 enhanced alpha5 expression.
  • ADAM15 overexpression significantly reduced lung metastasis in vivo.

Conclusions:

  • ADAM15 upregulates alpha5 integrin expression through the downregulation of phosphorylated Erk1/2.
  • This provides a novel mechanism for ADAM15 in regulating cell-matrix adhesion and migration.
  • ADAM15 plays a role in reducing pulmonary metastasis.

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