Elafin promotes tumour metastasis and attenuates the anti-metastatic effects of erlotinib via binding to EGFR in hepatocellular carcinoma.
Elafin promotes tumour metastasis and attenuates the anti-metastatic effects of erlotinib via binding to EGFR in hepatocellular carcinoma.
复制标题
在肝细胞癌中，Elafin 通过与 EGFR 结合促进肿瘤转移并减弱厄洛替尼的抗转移作用。
DOI：
10.1186/s13046-021-01904-y
复制
发表时间：
2021-03-26
期刊：
影响因子：
--
通讯作者：
Li B
中科院分区：
文献类型：
--
作者：
Wang C;Liao Y;He W;Zhang H;Zuo D;Liu W;Yang Z;Qiu J;Yuan Y;Li K;Zhang Y;Wang Y;Shi Y;Qiu Y;Gao S;Yuan Y;Li B
Elafin是一种丝氨酸蛋白酶抑制剂，对宿主防御至关重要。我们以前报道过Elafin与早期肝细胞癌（HCC）术后复发有关。然而，Elafin在HCC中的确切作用仍然不清楚。应用肝癌组织芯片研究Elafin表达与肝癌患者预后的关系。通过体外迁移、侵袭和伤口愈合试验以及体内肺转移模型来确定Elafin在HCC转移中的作用。通过质谱、免疫共沉淀、蛋白质印迹和免疫荧光染色等方法研究Elafin在肝癌中的作用机制。采用双荧光素酶报告基因和染色质免疫沉淀技术观察Elafin的转录调控作用。与正常组织相比，HCC组织中Elafin的表达经常增加，HCC组织中Elafin的高表达与HCC患者的侵袭性肿瘤表型和不良预后相关。Elafin通过与EGFR相互作用并激活EGFR/AKT信号通路，在体内外显著增强HCC细胞的转移。此外，Elafin减弱了厄洛替尼对HCC转移的抑制作用。此外，Elafin在肝癌细胞中受Sp1的转录调控。临床上，Elafin表达与Sp1、波形蛋白和EGFR信号在我们的HCC组织微阵列和TCGA数据库分析中呈正相关。Sp1上调Elafin可通过EGFR/AKT途径增强HCC转移，而Elafin过表达可减弱厄洛替尼的抗转移作用，提示Elafin是HCC的一个有价值的预后生物标志物和治疗靶点。在线版本包含补充材料，可在10.1186/s13046-021-01904-y获得。
Elafin is a serine protease inhibitor critical for host defence. We previously reported that Elafin was associated with the recurrence of early-stage hepatocellular carcinoma (HCC) after surgery. However, the exact role of Elafin in HCC remains obscure. HCC tissue microarrays were used to investigate the correlation between Elafin expression and the prognosis of HCC patients. In vitro migration, invasion and wound healing assays and in vivo lung metastasis models were used to determine the role of Elafin in HCC metastasis. Mass spectrometry, co-immunoprecipitation, western blotting, and immunofluorescence staining assays were performed to uncover the mechanism of Elafin in HCC. Dual-luciferase reporter and chromatin immunoprecipitation assays were employed to observe the transcriptional regulation of Elafin. Elafin expression was frequently increased in HCC tissues compared to normal tissues, and high Elafin expression in HCC tissues was correlated with aggressive tumour phenotypes and a poor prognosis in HCC patients. Elafin dramatically enhanced the metastasis of HCC cells both in vitro and in vivo by interacting with EGFR and activating EGFR/AKT signalling. Moreover, Elafin attenuated the suppressive effects of erlotinib on HCC metastasis. Besides, Elafin was transcriptionally regulated by Sp1 in HCC cells. Clinically, Elafin expression was positively correlated with Sp1, Vimentin, and EGFR signalling in both our HCC tissue microarrays and TCGA database analysis. Upregulation of Elafin by Sp1 enhanced HCC metastasis via EGFR/AKT pathway, and overexpression of Elafin attenuated the anti-metastatic effects of erlotinib, suggesting a valuable prognostic biomarker and therapeutic target for HCC. The online version contains supplementary material available at 10.1186/s13046-021-01904-y.
登录
查看更多内容
胆碱激酶 α 介导肝细胞癌细胞中表皮生长因子受体与雷帕霉素复合物 2 机制靶点之间的相互作用，促进耐药性和异种移植肿瘤进展
影响因子：
29.4
作者：
Lin XM;Hu L;Gu J;Wang RY;Li L;Tang J;Zhang BH;Yan XZ;Zhu YJ;Hu CL;Zhou WP;Li S;Liu JF;Gonzalez FJ;Wu MC;Wang HY;Chen L
通讯作者：
Chen L
影响因子：
13.5
作者：
Llovet, Josep M.;Bruix, Jordi
通讯作者：
Bruix, Jordi
影响因子：
4.8
作者：
Butler, Marcus W.;Robertson, Ian;McElvaney, Noel G.
通讯作者：
McElvaney, Noel G.
影响因子：
11.2
作者：
Caruso, Joseph A.;Hunt, Kelly K.;Keyomarsi, Khandan
通讯作者：
Keyomarsi, Khandan
影响因子：
11.2
作者：
Kong, Ling-Min;Liao, Cheng-Gong;Chen, Zhi-Nan
通讯作者：
Chen, Zhi-Nan