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- Title
The basic C-terminal amino acids of calcium-binding protein S100A4 promote metastasis.
- Authors
Thamir M. Ismail; David G. Fernig; Philip S. Rudland; Carla J. Terry; Guozheng Wang; Roger Barraclough
- Abstract
The calcium-binding protein S100A4 can induce a metastatic phenotype in animal model systems and its expression in various human cancers has been shown to be associated with metastasis and reduced patient survival. Using a series of nested deletion mutants, it is now shown that the two C-terminal lysine residues are required for the enhanced metastasis, invasion and migration abilities that S100A4 confers on cells in a model system of metastasis. Basic C-terminal residues enhance the affinity between S100A4 and its best characterized target, a recombinant C-terminal fragment of non-muscle myosin II heavy chain isoform A (NMMHC-IIA). In wild-type S100A4 protein, the presence of the C-terminal lysine, residue 101, enhances the rate of association between S100A4 and NMMHC-IIA. These results identify the amino acids of S100A4 that are involved in metastasis induction and show that the C-terminal region of S100A4 is a possible target for inhibitors of its metastatic action.
- Subjects
LYSINE; METASTASIS; CALCIUM-binding proteins; CANCER patients; SURVIVAL analysis (Biometry); ANIMAL models in research; THERAPEUTICS
- Publication
Carcinogenesis, 2008, Vol 29, Issue 12, p2259
- ISSN
0143-3334
- Publication type
Article
- DOI
10.1093/carcin/bgn217