转移是导致肝癌死亡率高的主要原因。细胞因子介导的转录因子激活在其中发挥关键的调控作用，然而分子机制不明。我们率先发现：①HOXC10在肝癌中的表达显著高于癌旁和正常肝组织，其过表达组患者复发率高生存率低；②上调HOXC10促进肝癌侵袭转移，下调HOXC10抑制肝癌侵袭转移；③HOXC10上调趋化因子CCL2、CCL5等表达；④IL-1β诱导HOXC10过表达，下调HOXC10表达显著抑制IL-1β导致的肝癌细胞侵袭和转移。提示：IL-1β-HOXC10途径可能在炎症相关肝癌转移中发挥重要作用。然而，IL-1β如何调控HOXC10表达？HOXC10上调哪些转移相关基因从而增强肝癌细胞的侵袭转移能力？HOXC10上调趋化因子表达招募哪些炎性细胞浸润改变肿瘤微环境？尚不清楚。本课题拟在前期工作基础上，通过细胞、裸鼠、条件敲除鼠等实验，阐明以上三个问题。研究有望为肝癌治疗提供新的靶点和策略。

Metastasis is the main reason for high recurrence and poor survival of hepatocellular carcinoma (HCC) after curative resection. Inflammation plays an important role in promoting HCC malignant progression and metastasis. However, little is known about molecular mechanisms underlying inflammation-associated HCC metastasis. Previously, we discovered that: ①HOXC10 expression was significantly increased in HCC tissues than in adjacent noncancerous tissues and normal liver tissues. HCC patients with high expression of HOXC10 had shorter overall survival of higher recurrence rates than those with low expression of HOXC10. ②Overexpression of HOXC10 promotes HCC invasion and metastasis, whereas knockdown of HOXC10 inhibited HCC invasion and metastasis. ③Overexpression of HOXC10 in HCC cells upregulated chemokines CCL2 and CCL5. ④Proinflammatory cytokines IL-1β induces HOXC10 expression in HCC cells, and knockdown of HOXC10 significantly decreased IL-1β-induced HCC invasion and metastasis. Based on these results, we hypothesized that IL-1β-HOXC10 signaling pathway may play an important role in inflammation related HCC metastasis. However, the molecular mechanism of HOXC10-mediated HCC metastasis and IL-1β-regulated HOXC10 overexpression remain still unknown. Do inhibition of IL-1β-HOXC10 signaling decrease HCC invasion and metastasis? In this study, these important questions will be explored by using HCC cell lines, nude mice model, conditional knockout mouse model and independent cohorts of human HCC tissues. These studies will not only discover the new function of HOXC10, but also provide potential candidate markers for HCC prognosis and therapeutic targets for HCC patients.