title: Collapsin response mediator protein 4 isoforms (CRMP4a and CRMP4b) have opposite effects on cell proliferation, migration, and invasion in gastric cancer.
abstract: Collapsin response mediator proteins (CRMPs) were originally identified in the nervous system and are involved in neuronal development. Similar to CRMP1, CRMP4 has a shorter transcript encoding a short isoform known as CRMP4a, and a longer transcript encoding a long isoform known as CRMP4b. Previous studies have shown that CRMP4a and CRMP4b exhibit opposing functions in neurite outgrowth. In the present study, we aimed to determine whether CRMP4a and CRMP4b have divergent effects in gastric cancer.
  
  
  
  We first analyzed the mRNA and protein expression levels of CRMP4a and CRMP4b in surgical resected specimens, gastric cancer cell lines and normal gastric epithelial cell line GES-1 by quantitative real-time PCR. Open reading frame and CRMP4b shRNA were generated by lentivirus package and stable cells stably expressing CRMP4a open reading frame and CRMP4b shRNA were constructed. Then the roles of CRMP4a and CRMP4b in cell proliferation, cell cycle progression, apoptosis, migration, invasion, and adhesion were determined by cell proliferation assays, flow cytometry analysis, transwell migration and invasion assays, cell Adhesion Assay, and tumorigenicity assays in nude mice, respectively.
  
  
  
  CRMP4a expression was lower and CRMP4b expression was higher in tumor tissue samples as compared to paired non-tumor tissue samples. Additionally, CRMP4a expression was lower and CRMP4b expression was higher in gastric cancer cell lines than in the normal gastric epithelial cell line GES-1. CRMP4a overexpression and CRMP4b silencing suppressed cell proliferation in vitro and in vivo. Additionally, CRMP4a overexpression and CRMP4b silencing induced a significant G1-phase arrest and a decrease of the percentage of cells in S-phase. Furthermore, CRMP4a overexpression and CRMP4b silencing inhibited cell migration, invasion, and adhesion. However, neither CRMP4a overexpression nor CRMP4b silencing affected apoptosis.
  
  
  
  These results indicate that CRMP4a and CRMP4b have opposite effects on cell proliferation, migration, and invasion in gastric cancer.
authors.affiliation: Department of gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People's Republic of China.|Department of gastroenterology, the Second People's Hospital of Shenzhen, Shenzhen, Guangdong, 518035, People's Republic of China.
authors.forename: Haijian
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People's Republic of China. bxia66@sina.com.
authors.forename: Bing
authors.initials: B
authors.lastname: Xia
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D020033:Protein Isoforms / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery
chemical_list: C102926:DPYSL3 protein, human; D009124:Muscle Proteins; D020033:Protein Isoforms
keywords: Collapsin response mediator protein 4; Gastric cancer; Opposite effects; Stable cells