肝癌发生侵袭转移是治疗效果差的重要原因，神经酰胺（Cer）抑制肿瘤侵袭转移，神经酰胺合成酶3（CerS3）是Cer合成的关键酶之一，其在肝癌中的作用未明。预实验发现肝癌组织CerS3表达降低；抑制CerS3后间质细胞标志物N-钙粘蛋白增加、Cer与SMAD6的相互作用减弱；高表达CerS3后N-钙粘蛋白降低，肝癌细胞的迁移、侵袭能力降低。为此，我们提出科学假说：肝癌CerS3表达下调→降低Cer水平→减弱Cer与SMAD6相互作用→降低SMAD6对TGF-β通路的抑制作用→增强TGF-β通路信号→促进EMT→肝癌发生侵袭转移。我们拟通过临床标本验证CerS3低表达促进肝癌侵袭转移，体外观察干预CerS3、SMAD6表达对肝癌细胞侵袭迁移能力的影响，体内研究干预CerS3表达对小鼠肝癌侵袭转移的影响。本研究有望阐明CerS3低表达与肝癌侵袭转移之间的关系及机制，为治疗肝癌侵袭转移寻求新靶点。

Invasion and metastasis of liver cancer is an important reason for the poor therapeutic effect. Ceramide (Cer) inhibits the invasion and metastasis of tumor, ceramide synthase 3 (CerS3) is one of the key enzymes in the synthesis of Cer, but the role of CerS3 in liver cancer remains unclear. Our preliminary data showed that the expression of CerS3 was decreased significantly in liver cancer. After CerS3 was inhibited, the mesenchymal cell marker N-cadherin was increased, and the interaction between Cer and SMAD6 was attenuated. Conversely, when CerS3 was highly expressed, the N-cadherin was decreased, and the migration and invasion ability of liver cancer cell was decreased. Therefore, we put forward a scientific hypothesis: low expression of CerS3 in liver cancer leads down-regulation of Cer, reduces the interaction between Cer and SMAD6, attenuates the inhibition of TGF-β signal via SMAD6, subsequently enhances TGF-β signals, and finally promotes EMT leading invasion and metastasis of liver cancer. We intend to verify that low expression of CerS3 promotes invasion and metastasis of liver cancer using clinic samples, in vitro observe the effect of inhibition or high expression of CerS3/SMAD6 on invasion and migration ability of liver cancer cells, and in vivo study the effect of inhibition or high expression of CerS3 on invasion and metastasis of liver cancer of mice. This study is expected to elucidate the relationship and mechanism between low expression of CerS3 and invasion and metastasis of liver cancer, and look for new targets for the treatment of invasion and metastasis of liver cancer.