课题组前期发现Intermedin(IMD)在肝癌患者的外周血和肿瘤组织中表达显著增高，与肿瘤侵袭和转移密切相关。抑制Rac1和CDC42活性可显著降低IMD诱导肝癌细胞丝状伪足形成；IMD可显著降低肝癌细胞Lamin蛋白mRNA水平，anti-IMD可增加Lamin蛋白转录，而Lamin蛋白是决定肿瘤细胞核刚性最重要的分子。基于文献和前期研究，我们推测“IMD可能通过Rac1/CDC42通路促进肝癌细胞丝状伪足的形成能力，从而提高其运动能力；同时，IMD还通过对Lamin蛋白的调控，降低肿瘤细胞核的刚性来提高肝癌细胞穿过狭窄孔隙的能力；IMD通过提升这两种能力，显著增强了肝癌细胞的侵袭和转移能力。”本研究首次结合IMD、Rac1/CDC42通路及Lamin蛋白，从细胞和整体水平探讨IMD在肝癌侵袭和转移过程中的分子机制，为筛选肝癌侵袭和转移的分子标志物提供理论基础和实验依据。

Our group found that Intermedin (IMD) was significantly over-expressed in the serum and hepatocellular carcinoma (HCC) tissues, and the level of IMD might be correlated with HCC invasion and metastasis. IMD-induced filopodia and migration of HCC cells were significantly decreased by depressing Rac1 and CDC42 activity. The Lamin protein was the most important molecule that determined the stiffness of nucleus. IMD significantly decreased the mRNA level of Lamin protein in HCC cells, and anti-IMD might increase Lamin protein transcription. According to literature reports and our previous work, we proposed that IMD might promote the formation of filopodiain in HCC cells through Rac1/CDC42 pathway, enhancing its migration ablitiy. Meanwhile, IMD could decrease stiffness of nucleus to enhance penetration ability in HCC cells by regulating Lamin protein. IMD significantly enhanced invasion and metastasis of HCC cells by these two ways. Combined with IMD, Rac1/CDC42 pathway and Lamin protein in HCC cells for the first time, the study aimed to investigate the IMD molecular mechanism of promotion on HCC invasion and metastasis from the cell level and the overall level comprehensively, which would be conducive to provide new insight into screening biomarkers for diagnosis and treatment on HCC invasion and metastasis.