CEACAM1 functionally interacts with filamin A and exerts a dual role in the regulation of cell migration

J Cell Sci. 2005 Dec 1;118(Pt 23):5513-24. doi: 10.1242/jcs.02660. Epub 2005 Nov 15.

Abstract

The carcinoembryonic antigen-related cell adhesion molecule CEACAM1 (CD66a) and the scaffolding protein filamin A have both been implicated in tumor cell migration. In the present study we identified filamin A as a novel binding partner for the CEACAM1-L cytoplasmic domain in a yeast two-hybrid screen. Direct binding was shown by surface plasmon resonance analysis and by affinity precipitation assays. The association was shown for human and rodent CEACAM1-L in endogenous CEACAM1-L expressing cells. To address functional aspects of the interaction, we used a well-established melanoma cell system. We found in different migration studies that the interaction of CEACAM1-L and filamin A drastically reduced migration and cell scattering, whereas each of these proteins when expressed alone, acted promigratory. CEACAM1-L binding to filamin A reduced the interaction of the latter with RalA, a member of the Ras-family of GTPases. Furthermore, co-expression of CEACAM1-L and filamin A led to a reduced focal adhesion turnover. Independent of the presence of filamin A, the expression of CEACAM1-L led to an increased phosphorylation of focal adhesions and to altered cytoskeletal rearrangements during monolayer wound healing assays. Together, our data demonstrate a novel mechanism for how CEACAM1-L regulates cell migration via its interaction with filamin A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / pharmacology
  • Antigens, CD / physiology*
  • Cell Adhesion / drug effects
  • Cell Adhesion / physiology
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / pharmacology
  • Cell Adhesion Molecules / physiology*
  • Cell Line, Tumor
  • Cell Movement / physiology*
  • Contractile Proteins / genetics
  • Contractile Proteins / physiology*
  • Cytoskeleton / drug effects
  • Cytoskeleton / metabolism
  • Filamins
  • Focal Adhesion Protein-Tyrosine Kinases / drug effects
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism
  • Gene Expression Regulation
  • Humans
  • Microfilament Proteins / genetics
  • Microfilament Proteins / physiology*
  • Paxillin / drug effects
  • Paxillin / metabolism
  • Phosphorylation
  • Protein Binding
  • Rats
  • Two-Hybrid System Techniques
  • Tyrosine / drug effects
  • Tyrosine / metabolism

Substances

  • Antigens, CD
  • CD66 antigens
  • Cell Adhesion Molecules
  • Contractile Proteins
  • Filamins
  • Microfilament Proteins
  • Paxillin
  • Tyrosine
  • Focal Adhesion Protein-Tyrosine Kinases