Characterization of Molecular Factors Critical to the S100A4 (A Metastasis-Associated Protein) - Dependent Increase in Motility of Breast Cancer Cells
Abstract
Our studies show that S100A4 localizes to lamellipodia structures in a migrating breast cancer-derived cell line and colocalizes with a known S100A4-interacting protein, heavy chain IIA (MHC-IIA) at the leading edge. We also demonstrate that S100A4 mutants that are either defective in their ability to dimerize or calcium-binding are unable to interact with MHC-IIA. An S100A4 mutant that is deficient for calcium-binding retains the ability to form homodimers, suggesting that S100A4 can exist as calcium-free or calcium-bound dimmers in vivo. Interestingly, despite the calcium-dependence for interaction with known protein partners, calcium-binding is not necessary for localization to lamellipodia. Both wild type and a mutant that is deficient for calcium-binding colocalize with known markers of actively forming leading edges of lamellipodia, Arp3, and N-WASP. These data suggest that S100A4 localizes to the leading edge in a calcium-independent manner and identification of the proteins that are involved in localizing S100A4 to the lamellipodial structures will provide novel insight into the mechanism by which S100A4 participates in metastasis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2004
- Accession Number
- ADA424207
Entities
People
- David Helfman
- Edward J. Kim
Organizations
- Cold Spring Harbor Laboratory