B O Wu1, Wen G Jiang2, Deshan Zhou3, Yu-Xin Cui4. 1. 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. 2. Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, U.K. 3. 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. 4. Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, U.K. cuiy7@cf.ac.uk.
Abstract
BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: EPHA1 suppresses spreading and adhesion of HRT18 colorectal cancer cells through deactivation of ERK and JNK signaling pathways. Copyright
BACKGROUND: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. MATERIALS AND METHODS: In this study, we investigated the expression profile of EPHA1 in humancolorectal cancer and its effect on the adhesion and motility of colorectal cancer cells. We used humancolorectal cancer specimens and the colorectal adenocarcinoma cell line HRT18 for this purpose. RESULTS: 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. CONCLUSION:EPHA1 suppresses spreading and adhesion of HRT18 colorectal cancer cells through deactivation of ERK and JNK signaling pathways. Copyright
Authors: Julia Rudno-Rudzińska; Wojciech Kielan; Ewelina Frejlich; Krzysztof Kotulski; Wojciech Hap; Krzysztof Kurnol; Przemysław Dzierżek; Marcin Zawadzki; Agnieszka Hałoń Journal: Chin J Cancer Res Date: 2017-08 Impact factor: 5.087