Wu B O, Jiang Wen G, Zhou Deshan, Cui Yu-Xin
Department of Histology and Embryology, Capital Medical University, Beijing, P.R. China Cancer Institute, Capital Medical University, Beijing, P.R. China Key Laboratory of Cancer Metastasis (Beijing), Capital Medical University, Beijing, P.R. China Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, U.K.
Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, U.K.
Anticancer Res. 2016 Mar;36(3):1211-9.
Erythropoietin-producing hepatocellular A1 (EPHA1) is the first member of the EPH superfamily. Its abnormal expression has been reported in various cancer types. However, the contribution of EPHA1 to the regulation of colorectal cancer cell behaviour remains unknown.
In this study, we investigated the expression profile of EPHA1 in human colorectal cancer and its effect on the adhesion and motility of colorectal cancer cells. We used human colorectal cancer specimens and the colorectal adenocarcinoma cell line HRT18 for this purpose.
Our cohort screening data showed that in patients with colorectal cancer, low expression of EPHA1 gene is correlated with a remarkably reduced survival. After EPHA1 is knocked-down in colorectal cancer cells using a clustered regularly interspaced short palindromic repeats-associated nuclease 9 (CRISPR-CAS9) genomic editing system, we observed an increase in the spreading and adhesion of HRT18 cells. Moreover, protein array data indicated that the extracellular-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) signaling pathways were activated as a consequence. Inhibition of ERK and JNK proteins with specific inhibitors led to suppression of migration of the colorectal cancer cells.
EPHA1 suppresses spreading and adhesion of HRT18 colorectal cancer cells through deactivation of ERK and JNK signaling pathways.
促红细胞生成素产生肝细胞A1（EPHA1）是EPH超家族的首个成员。其异常表达已在多种癌症类型中被报道。然而，EPHA1对结直肠癌细胞行为调控的作用仍不清楚。
在本研究中，我们调查了EPHA1在人结直肠癌中的表达谱及其对结直肠癌细胞黏附和运动的影响。我们为此使用了人结直肠癌标本和结直肠腺癌细胞系HRT18。
我们的队列筛查数据显示，在结直肠癌患者中，EPHA1基因低表达与生存率显著降低相关。使用成簇规律间隔短回文重复序列相关核酸酶9（CRISPR-CAS9）基因组编辑系统在结直肠癌细胞中敲低EPHA1后，我们观察到HRT18细胞的铺展和黏附增加。此外，蛋白质阵列数据表明，细胞外调节激酶（ERK）和c-Jun氨基末端激酶（JNK）信号通路因此被激活。用特异性抑制剂抑制ERK和JNK蛋白导致结直肠癌细胞迁移受到抑制。
EPHA1通过使ERK和JNK信号通路失活来抑制HRT18结直肠癌细胞的铺展和黏附。
