Mutually antagonistic actions of S100A4 and S100A1 on normal and metastatic phenotypes.
Increased levels of the homodimeric calcium-binding protein, S100A4, have been shown to cause a metastatic phenotype in at least three independent model systems of breast cancer and its presence in carcinoma cells has been shown to be associated with a reduction in the survival of patients suffering from a range of different cancers. S100A4 has been shown to interact in vitro with another member of the S100 family of proteins, S100A1. The purpose of the present study was to find out whether S100A1 could affect S100A4 function. Fluorescence resonance energy transfer was used to show the interaction of S100A4 and S100A1 in living cells and the binding affinities between S100A4 and S100A1 were determined using a biosensor. S100A1 reduced the S100A4 inhibition of nonmuscle myosin A self-association and phosphorylation in vitro. S100A1 reduced S100A4 induced motility and growth in soft agar and metastasis in vivo. The results show for the first time that interactions between different S100 proteins can affect cancer-related activity, and that the presence of S100A1 protein in carcinoma cells might modulate the effect of S100A4 on their metastatic abilities.
Wang
Guozheng
G
School of Biological Sciences, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK.
Zhang
Shu
S
Fernig
David G
DG
Martin-Fernandez
Marisa
M
Rudland
Philip S
PS
Barraclough
Roger
R
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002465:Cell Movement / Q000235:genetics; D005260:Female; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D020409:Molecular Motor Proteins / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010641:Phenotype; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D015854:Up-Regulation
D002135:Calcium-Binding Proteins; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D012333:RNA, Messenger; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C110294:S100A1 protein; C499412:S100a4 protein, rat; C077591:S100A4 protein, human; D018995:Myosin Heavy Chains