The C-terminal region of S100A4 is important for its metastasis-inducing properties
- 18 April 2005
- journal article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 24 (27), 4401-4411
- https://doi.org/10.1038/sj.onc.1208663
Abstract
The EF-hand protein, S100A4, binds calcium ions and interacts specifically in vitro with protein targets. Elevated levels of S100A4 have been shown to produce a metastatic phenotype in independent models of breast cancer. The presence of S100A4 in the carcinoma cells of patients with different carcinomas is associated with reduced patient survival. In order to identify the region of the S100A4 molecule that is responsible for its metastasis-inducing properties, specific mutant S100A4 genes and proteins have been produced which contain targeted mutations to the two calcium-binding sites and a deletion of the last 15 amino-acid residues of the protein. The ability of the mutant proteins to bind to a potential specific target in vitro, nonmuscle myosin heavy chain, is correlated with their ability to cause motile, invasive and metastatic phenotypes. Mutation of the C-EF hand of S100A4 virtually abolished calcium binding, and motility/invasion in vitro, abolished interaction with a molecular target, and reduced metastasis induction by 2.5-3-fold. However, deletion of the last 15 amino acids of S100A4 reduced motility/invasion, target binding and metastasis-induction to similar extents as the C-EF-hand mutant, but reduced calcium binding by only 26%. The results suggest that the ability to interact with protein target(s) is important in S100A4-induced metastasis.Keywords
This publication has 32 references indexed in Scilit:
- Erratum to “Binding to Intracellular Targets of the Metastasis-Inducing Protein, S100A4 (p9Ka)” [Biochem. Biophys. Res. Commun. 286 (2001) 1212–1217]Biochemical and Biophysical Research Communications, 2003
- Expression of S100A4 protein is associated with metastasis and reduced survival in human bladder cancerThe Journal of Pathology, 2002
- Binding to Intracellular Targets of the Metastasis-Inducing Protein, S100A4 (p9Ka)Biochemical and Biophysical Research Communications, 2001
- Interaction in Vivo and in Vitro of the Metastasis-inducing S100 Protein, S100A4 (p9Ka) with S100A1Published by Elsevier BV ,2000
- Interaction of Heparan Sulfate from Mammary Cells with Acidic Fibroblast Growth Factor (FGF) and Basic FGFPublished by Elsevier BV ,1998
- Effect of Mts1 on the Structure and Activity of Nonmuscle Myosin IIBiochemistry, 1997
- CorrigendumJournal of Bone and Mineral Research, 1995
- Calvasculin, as a factor affecting the microfilament assemblies in rat fibroblasts transfected by src geneFEBS Letters, 1993
- Calcium-ion binding by the potential calcium-ion-binding protein, p9KaBiochemical and Biophysical Research Communications, 1990
- Site-directed mutagenesis by overlap extension using the polymerase chain reactionGene, 1989