炎症微环境与肿瘤细胞的交叉对话是促进肝癌（HCC）演进和耐药的关键机制。本课题组前期研究发现Jab1/p57是调控HCC发生发展重要的细胞内调控途径，文献报道炎症微环境的关键通路IL-6/STAT3和IGF可以调控Jab1的转录激活。由此推测：HCC炎症微环境可能通过HCC细胞内的Jab1/p57途径实现与肿瘤细胞的交叉对话，影响其恶性生物学行为；阻断上述炎症通路可逆转Jab1/p57表达，抑制炎症微环境对肿瘤细胞的持续激活。本课题拟在临床病理、动物模型、体外细胞三个层面，应用生物信息数据库、临床数据分析、转基因动物、细胞行为学、组织体液芯片、小动物成像等方法分析炎症微环境中IL6/STAT3和IGF通路对Jab1/p57的调控关系，阐明炎症微环境-肿瘤细胞交叉对话的新机制；探索IL6/STAT3和IGF通路阻断逆转Jab1/p57表达、抑制肿瘤演进的可能性，为HCC治疗提供新的靶向药物。

It is the key mechanism that crosstalk between inflammatory microenvironment and tumor cells to promote HCC progression and drug resistance. We had found that Jab1/p57 is an important intracellular pathway in regulating HCC development. It is reported that the key pathways, IL-6/STAT3 and IGF, in the inflammatory microenvironment can regulate the transcriptional activation of Jab1. Therefore, we speculate that HCC inflammatory microenvironment may crosstalk with HCC cells via Jab1/p57 pathway and affect the biological behaviors of HCC; Blocking the inflammatory pathways can reverse Jab1/p57 expression and inhibit the positive feedback between inflammatory microenvironment and tumor cells. To confirm the hypothesis, we will use biological information database, clinical data analysis, transgenic animal models, cell behaviors and chips on three levels, to demonstrate the regulation of IL6/STAT3 and IGF pathways on Jab1/p57, to elucidate the new mechanism of inflammatory microenvironment-tumor cells crosstalk, to explore the possibility via blocking of IL6/STAT3 and IGF pathway to reverse Jab1/p57 expression and inhibit tumor progression, and to provide a possible targeted drug for HCC treatment.