C1orf61 is a specific transcriptional activator that is highly up-regulated during weeks 4–9 of human embryogenesis, the period in which most organs develop. We have previously demonstrated that C1orf61 acts as a tumor activator in human hepatocellular carcinoma (HCC) tumorigenesis and metastasis. However, the underlying molecular mechanisms of tumor initiation and progression in HCC remain obscure. In this study, we demonstrated that the pattern of C1orf61 expression was closely correlated with metastasis in liver cancer cells. Gene expression profiling analysis indicated that C1orf61 regulated diverse genes related to cell growth, migration, invasion and epithelial-mesenchymal transition (EMT). Results showed that C1orf61 promotes hepatocellular carcinoma metastasis by inducing cellular EMT in vivo and in vitro. Moreover, C1orf61-induced cellular EMT and migration are involved in the activation of the STAT3 and Akt cascade pathways. In addition, C1orf61 expression improved the efficacy of the anticancer therapy sorafenib in HCC patients. For the first time, we report a regulatory pathway by which C1orf61 promoted cancer cell metastasis and regulated the therapeutic response to sorafenib. These findings increased our understanding of the molecular events that regulate metastasis and treatment in HCC.

C1orf61 是一种特定的转录激活因子，在人类胚胎发生的第 4-9 周（大多数器官发育的时期）高度上调。我们之前已经证明 C1orf61 在人肝细胞癌 (HCC) 肿瘤发生和转移中充当肿瘤激活剂。然而，HCC 中肿瘤发生和进展的潜在分子机制仍不清楚。在这项研究中，我们证明了 C1orf61 的表达模式与肝癌细胞的转移密切相关。基因表达谱分析表明，C1orf61 调节与细胞生长、迁移、侵袭和上皮间质转化 (EMT) 相关的多种基因。结果表明，C1orf61通过在体内外诱导细胞EMT促进肝细胞癌转移。而且，C1orf61 诱导的细胞 EMT 和迁移参与了 STAT3 和 Akt 级联通路的激活。此外，C1orf61 的表达提高了抗癌疗法索拉非尼在 HCC 患者中的疗效。我们首次报告了 C1orf61 促进癌细胞转移并调节对索拉非尼的治疗反应的调节途径。这些发现增加了我们对调节 HCC 转移和治疗的分子事件的理解。