title: Knockdown of EPHA1 by CRISPR/CAS9 Promotes Adhesion and Motility of HRT18 Colorectal Carcinoma Cells.
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.
  
  
  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.
  
  
  CONCLUSIONS
  EPHA1 suppresses spreading and adhesion of HRT18 colorectal cancer cells through deactivation of ERK and JNK signaling pathways.
authors.affiliation: 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.
authors.forename: B O
authors.initials: BO
authors.lastname: Wu
authors.affiliation: Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, U.K.
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
authors.affiliation: 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.
authors.forename: Deshan
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, U.K. cuiy7@cf.ac.uk.
authors.forename: Yu-Xin
authors.initials: YX
authors.lastname: Cui
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D064113:CRISPR-Cas Systems; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D048430:Cell Shape; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D009361:Neoplasm Invasiveness; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D036082:Receptor, EphA1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
chemical_list: D047428:Protein Kinase Inhibitors; D036082:Receptor, EphA1; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases
keywords: CAS9; CRISPR; EPHA1; adhesion; colorectal carcinoma cells; motility