A New Invasion and Metastasis Molecule, TIAMI1, and Its Interaction with the Cytoskeleton are Involved in Human Breast Cancer Progression
Abstract
We have investigated the interaction between Tiam1 and CD44 (the hyaluronic acid (HA) binding receptor in breast tumor cells (SPl cell line). Our data indicate that both the Tiaml protein and the CD44v3 isoform are expressed in SPl cells, and that these two proteins are physically associated as a complex in vivo. Using calmodulin-binding peptide (CBP)-tagged Tiam1 fragment I.E., THE NH2-terminal pleckstrin homology (PHn) domain and an adjacent protein interaction domain (designated as PHn-CC-Ex, aa393-aa738 of Tiam1 and an in vitro binding assay, we have detected a specific binding interaction between the Tiaml's PHn-CC-Ex domain and CD44. The binding of HA to CD44v3 of SPl cells stimulates Tiam1-catalyzed Racl signaling and cytoskeleton-mediated tumor cell migration. Transfection of SPl cells with Tiam1cDNA promotes Tiam1 association with CD44v3 and upregulates Racl signaling as well as HA/CD44v3-mediated breast tumor cell migration. Co-transfection of SPl cells with PHn-CC-ExcDNA and TaimlcDNA effectively inhibits Tiaml association with CD44 and efficiently blocks tumor behaviors. Taken together, we believe that the linkage between CD44v3 isoform and the PHn-CC-EX domain of Tiaml is required for HA stimulated Racl signaling and cytoskeleton mediated tumor cell migration during breast cancer progression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1999
- Accession Number
- ADA376471
Entities
People
- Lilly Y. Bourguignon
Organizations
- University of Miami