上皮细胞可塑性在肝癌进程中起到重要作用，但其调控网络并不明确，且在体内模型中少有研究。申请人前期研究表明，“炎-癌链”中细胞因子TGF-β可与肝癌抗原CD147形成正反馈环路，调控肝细胞/肝癌细胞细胞可塑性。然而，TGF-β与CD147相互调节的具体机制尚未阐明；在动物体内肝癌模型中，TGF-β-CD147环路是否通过调节细胞可塑性推进肝癌进程；TGF-β-CD147环路能否成为新的肝癌防治靶标——这些问题有待深入探讨。.本课题将首先在细胞系水平明确TGF-β-CD147环路对肝细胞/肝癌细胞可塑性及恶性行为的影响，阐明TGF-β与CD147相互调控机制；构建肝细胞特异性敲除Basigin/CD147基因小鼠，建立化学诱导肝癌模型，探讨TGF-β-CD147环路在肝癌进展及肝癌细胞可塑性调控中的作用；并以TGF-β-CD147环路为靶点，研究通过调节肝癌细胞可塑性阻抑肝癌进程的可能性。

Cellular plasticity plays an important role in the progression of hepatocellular carcinoma, with the molecular mechanisms regulating plasticity of cells remains unclear. Our previous study has revealed a positive feedback loop between transforming growth factor beta (TGF-β) and CD147, which promotes the epithelial-mesenchymal transition (EMT) of hepatic cells and dedifferentiation of hepatoma cells. However, the mechanism underlying TGF-β-CD147 loop has not been completely understood. Moreover, we want to explore whether or not TGF-β-CD147 loop exists in the DEN-induced HCC model and promotes HCC progression via regulating cellular plasticity. TGF-β-CD147 loop may serve as a potential target for differentiation therapy of HCC..This study will firstly confirm the role of TGF-β-CD147 loop in regulating cellular plasticity and enhancing malignancy of cells, and the mechanism underlying the loop will be explored. HCC will be induced in the hepatocyte-specific Basigin/CD147 knockout mice and control mice by mutation inducer DEN combined with tumor enhancer PB to examine the role of TGF-β-CD147 loop in plasticity regulation and progression of HCC in vivo. Finally, we will also try to study the potential of TGF-β-CD147 loop as a target for repressing the carcinogenesis and development of HCC.