Chen H, Fernig D G, Rudland P S, Sparks A, Wilkinson M C, Barraclough R
Molecular Medicine Research Group, University of Liverpool, Liverpool, L69 7ZB, United Kingdom.
Biochem Biophys Res Commun. 2001 Sep 7;286(5):1212-7. doi: 10.1006/bbrc.2001.5517.
Experimentally elevated levels of S100A4 induce a metastatic phenotype in benign mammary tumour cells in vivo. In humans, the presence of S100A4 in breast cancer cells correlates strongly with reduced patient survival. Potential interacting binding partners for S100A4 have now been examined using an optical biosensor. There was significant interaction of S100A4 with non-muscle myosin and p53, but not with actin, tropomyosin or tubulin. The results suggest that myosin and p53 are likely to be intracellular targets of S100A4. S100A4 had a greater affinity for wild-type or mutant arg-175-his p53 than for non-muscle myosin. The results suggest that S100A4 might induce metastasis by influencing the function of p53 as well as through its interaction with myosin and that any mechanism is independent of the mutational status of p53.
实验性提高的S100A4水平在体内可诱导良性乳腺肿瘤细胞出现转移表型。在人类中，乳腺癌细胞中S100A4的存在与患者生存率降低密切相关。现在已使用光学生物传感器检测了S100A4潜在的相互作用结合伴侣。S100A4与非肌肉肌球蛋白和p53存在显著相互作用，但与肌动蛋白、原肌球蛋白或微管蛋白无相互作用。结果表明，肌球蛋白和p53可能是S100A4的细胞内靶点。S100A4对野生型或突变型精氨酸-175-组氨酸p53的亲和力比对非肌肉肌球蛋白的亲和力更高。结果表明，S100A4可能通过影响p53的功能以及通过其与肌球蛋白的相互作用来诱导转移，并且任何机制均与p53的突变状态无关。
