CTHRC1经PI3K/AKT/CREB(Snail)信号通路促进肝细胞癌侵袭和转移机制的研究

Background & Aims:CTHRC1 expression is associated with invasion and metastasis in various tumors. However, the functional role and signaling pathway of CTHRC1 in hepatocellular carcinoma (HCC) remains elucidative. The purpose of this study was to to elucidate the underlying signaling pathway(s) and to determine the significance of serum levels of CTHRC1 in diagnosis of HCC. .Methods: CTHRC1 protein expression was investigated by immunoblotting analysis in HCC cell lines and HCC tissues. Secreted CTHRC1 were also examined in the serum of HCC patients.The patients serum AFP and serum CTHRC1 were measured by Fluorescent enzyme-linked immunosorbent assay. The migration and invasion abilities of HepG2 cells stably expressing CTHRC1 was assessed in vitro. Moreover, signaling pathways involved in invasion and metastasis were analyzed by Western blotting. .Results:CTHRC1 was abundantly expressed in HCC cell lines and HCC tissues. CTHRC1 was detectable in the serum of HCC patients, compared with controls. CTHRC1 is more sensitive than AFP in diagnosis of HCC detection in patients .Ectopic expression of CTHRC1 in HepG2 cells promotes cell migration and invasiveness in vitro, Activation of the PI3K/Akt/CREB and PI3K/Akt/Snail pathways are required for CTHRC1-mediated EMT change and metastasis of HCC cells. .Conclusions:CTHRC1 is preferentially expressed in hepatocellular carcinoma. CTHRC1 could improve the diagnostic value for HCC. CTHRC1 promotes cancer cell invasiveness and metastasis through activation of PI3K/Akt/ CREB and PI3K/Akt/ Snail pathways, which induce EMT change.Therefore, CTHRC1 can serve as a marker for screening HCC.CTHRC1 may be a potential therapeutic target in HCC progression.

CTHRC1与多种肿瘤细胞的侵袭和转移相关，然而在肝细胞癌中所扮演的角色及信号通路尚待研究。本课题的目的是研究其潜在的信号通路及评价血清CTHRC1在肝细胞癌中的诊断价值。通过免疫印记检测肝癌组织，肝癌细胞系及病人血清中CTHRC1的表达，荧光酶联免疫吸附试验评估其诊断价值。建立过表达CTHRC1的HepG2细胞株，检测细胞侵袭和转移的能力，并探索和侵袭转移相关的信号通路及分子机制。我们发现CTHRC1在多数肝癌细胞株和肝癌组织中都高表达，在病人血清中明显升高，并且血清CTHRC1的诊断价值优于AFP。过表达CTHRC1能促进HepG2细胞的侵袭和转移能力，并可能通过激活PI3K/Akt/CREB 和 PI3K/Akt/Snail信号通路，影响EMT的发生，进而促进肝癌的侵袭和转移。因此，作为一个潜在的肝癌血清标记物，CTHRC1具有较高的临床诊断价值并能为肝癌靶向性基因治疗提供新靶点。