“循环播散转移”及“门脉癌栓形成”为肝细胞癌最常见的两大转移模式。癌细胞“上皮-间叶转化（EMT）”可赋予其高转移潜能已被公认；Tiam1分子状态变化则可影响癌细胞转移模式。我们前期研究发现：S100P/BCAT1异质表达于肝癌不同细胞亚群中，两者均能正向调控EMT过程，但对Tiam1分子状态调控却呈相反趋势。此外，高表达S100P的肝癌患者门脉癌栓的发生率高；高表达BCAT1的患者外周循环肿瘤细胞数量明显升高。推测S100P/BCAT1对肝癌转移模式的调控可能分别具有特殊意义，但机理未明。本项目拟在此基础上，通过临床大样本进一步论证S100P/BCAT1高表达与门脉癌栓发生及循环肿瘤细胞生成的关系；通过构建细胞/动物模型探讨两者高表达对肝癌细胞转移潜能的影响；最后分子水平深入解析两者对EMT及Tiam1分子状态的调控作用及机理。本研究将为不同转移模式肝癌患者的精准治疗提供新靶点与新思路。

"Circulating metastasis" and "portal vein tumor thrombus formation" are two most common metastatic patterns of hepatocellular carcinoma(HCC). It has been recognized that epithelial-mesenchymal transition (EMT) can give tumor cells high potential ability of metastasis，and the change of Tiam1 molecule state may affect the metastatic pattern of cancer cells. Our previous study suggested that: S100P/BCAT1 over-expressed in different cells of primary tumor of HCC, both of which could positively regulate EMT process, but the regulation of Tiam1 molecular state was reversed. In addition, patients with high BCAT1 expression had high circulation tumor cells count; and the high incidence of portal vein tumor thrombus was found in patients with high S100P expression. Therefore, it is assumed that S100P/BCAT1 may have special significance in the regulation of different metastatic patterns of HCC, while the mechanism is still unclear. Based on previous studies，we first further demonstrated the relationship between S100P/BCAT1 and portal vein tumor thrombus /and circulating tumor cells through clinical large samples. Then, experiments in vivo and in vitro will be perform to investigate effects of both S100P/BCAT1 on metastasis potential; Finally, regulatory mechanism of S100P/BCAT1 on the the "EMT" and the "Tiam1 molecular state" were analyzed from the molecular level. This study will provide new targets and new ideas for precision treatment of different metastatic HCC patients.