生命科学联合中心
学术报告
题 目: S100 protein family in human cancer metastasis.
报告人: Zhihua Liu,, Ph.D.
State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, China
时 间: 2012年4月22日（星期一），下午 13:00-14:00 pm
地 点: 北京大学新生物楼邓佑才报告厅
联系人: 生命科学联合中心，孔道春（Tel：6276-0866）
相关下载：Zhihua Liu CV; 参考文献1；参考文献2；
Metastasis is the most important feature of malignant tumors, and it is the leading cause of cancer death, almost 90% of cancer patients died of metastasis. S100 protein family has been implicated in multiple stages of tumorigenesis and progression. Among the S100 genes, 22 are clustered at chromosome locus 1q21, a region frequently rearranged in cancers. S100 protein possesses a wide range of intracellular and extracellular functions such as regulation of calcium homeostasis, cell proliferation, apoptosis, cell invasion and motility, cytoskeleton interactions, protein phosphorylation, regulation of transcriptional factors, autoimmunity, and chemotaxis etc. Many lines of evidence suggest that altered S100 protein expression was associated with tumor progression and poor prognosis. Therefore, S100 might also represent potential tumor biomarkers and therapeutic targets.
Almost all of the S100 proteins except S100A7 were down-regulated in human esophageal squamous cell carcinoma (ESCC), we showed that S100A14 promotes cell motility and invasiveness by regulating the expression and function of MMP2 in a p53-dependent manner. We found that, as a transcription factor, p53 could regulate the expression of S100A14, and S100A14 could affect p53 transactivity and stability, therefore, a feedback loop exists between p53 and S100A14. Moreover, we demonstrated that S100A14 binds directly to HER2 by co-immunoprecipitation and pull down assays. Further study shows that residues 956-1154 of HER2 intracellular domain and the C-terminal EF hand of S100A14 are essential for the two proteins binding, S100A14 functions as a modulator of HER2 signaling. We also found significantly increased S100A14 serum levels in breast cancer patients in comparison with healthy controls or patients suffering from benign breast disease, therefore, S100A14 could be served as a serum tumor biomarker, and S100A14 is significantly associated with outcome of breast cancer patients.
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