转移是肝细胞肝癌致死的关键原因，明确转移的分子机制，对于有效防控肝癌转移，提高患者存活率，具有重大意义。申请者通过分析TCGA公共数据库发现TCF19在肝癌中显著高表达，但其在肝癌中的功能尚未见报道。对140例肝癌样本进行免疫组化分析，显示TCF19与患者的复发转移呈显著正相关。进一步我们发现：过表达TCF19可诱导肝癌细胞发生EMT，增强肝癌细胞的侵袭迁移能力及抗凋亡和非锚定依赖性生长能力。相关机制研究提示TCF19通过上调Wnt/β-Catenin信号通路活性，在肝癌转移中发挥重要作用。据此，申请者拟深入研究TCF19激活Wnt/β-Catenin信号通路的分子机制，并结合临床样本研究TCF19及其调控分子与肝癌复发转移的相关性。以上研究结果有助于阐明TCF19促进肝癌复发转移的具体分子机制，提供新的临床预警分子，并丰富Wnt/β-Catenin信号通路在肝癌中异常激活的新的调控机制。

Hepatocellular carcinoma (HCC) is a common and aggressive cancer, with an increasing incidence globally, especially in China. It’s important to clarify the molecular mechanism and key regulators of HCC metastasis, which will effectively control the metastasis of HCC and improve the survival rate of HCC patients. Recently, We assessed the expression of TCF19 in multiple HCC cell lines and tissue, as well as the HCC dataset from TCGA. We found that TCF19 was overexpressed in HCC, and the overall expression level of TCF19 significantly correlated with lymph node metastasis (p<0.001) and distant metastasis (p<0.001), suggesting that TCF19 was involved in HCC metastasis. Furthermore, our preliminary data showed that overexpression of TCF19 induced epithelial-mesenchymal transition, inhibited apoptosis, promoted anchorage-independent growth. Further mechanism studies demonstrated that TCF19 could active the Wnt/β-Catenin pathway. These results suggested that TCF19 might play an important role in HCC metastasis. In the current project, we will combine in vivo and in vitro experimental systems, as well as clinical samples to clarify the molecular mechanism that TCF19 active the Wnt/β-Catenin pathway and clinical relevance. This work may identify novel indicator markers for HCC metastasis and also enrich the regulatory mechanism of Wnt/β-Catenin signaling pathway in HCC.