肝细胞癌是我国常见恶性肿瘤之一。我们前期研究证实DDR2和ACK1在肝癌中存在过表达现象，且DDR2可能是ACK1的下游因子，但具体作用机制不明。既往研究表明IL-6作为一个重要炎症因子，可以通过调控下游IL-6/STAT3通路进而促进肝癌的发生。我们的前期工作也发现IL-6/STAT3通路可以上调ACK1的表达，但其在HCC中具体机制以及如何通过下游因子调节 HCC 生长和转移的，目前仍不清楚。本研究是对既往工作的深入，拟通过组织学及体内外实验证实DDR2是炎症信号通路IL-6/STAT3/ACK1的一个下游靶点，IL-6/STAT3/ACK1通路可以通过调控DDR2进而激活下游ERK、AKT信号通路，促进EMT及上调BAD、Caspase 9和FKHRL 1磷酸化水平，从而参与HCC的发生发展。本项目将为HCC的靶向治疗及诊断预后标志物的发现提供实验依据。

Hepatocellular carcinoma (HCC) is one of the most common malignant tumor in China. Our previous study have shown that the expression of DDR2 and ACK1 were obviously higher in HCC tissues than that in non-tumor tissues and DDR2 may be a downstream target of ACK1, but the role and mechanisms are still unknown. Previous studies have shown that inflammation plays a key role in the hepatocarcinogenesis. As an important inflammatory factor, IL-6 can promote the hepatocarcinogenesis by regulating the downstream pathway IL-6/STAT3, but the exact mechanism of IL-6-associated hepatocarcinogenesis still remains unclear. In our present project, we try to determine whether DDR2 acts as a downstream target of IL-6/STAT3/ACK1 inflammatory signaling pathway, and IL-6/ACK1 signaling can activate the downstream ERK and AKT signaling pathways by regulating DDR2, and promote EMT and up regulation of BAD, Caspase9 and FKHRL1 phosphorylation. Furthermore, we attempt to elucidate the molecular mechanism of DDR2 in the hepatocarcinogenesis mediated by inflammation. The aim of this study is to investigate the molecular mechanisms of DDR2, in order to provide the scientific basis to exploit novel targeting agents and predictive biomarkers for HCC patients.