title: RON kinase isoforms demonstrate variable cell motility in normal cells.
abstract: BACKGROUND
  Aberrant RON (Recepteur d'Origine Nantais) tyrosine kinase activation causes the epithelial cell to evade normal growth pathways, resulting in unregulated cell proliferation, increased cell motility and decreased apoptosis. Wildtype (wt) RON has been shown to play a role in metastasis of epithelial malignancies. It presents an important potential therapeutic target for colorectal, breast, gastric and pancreatic cancer. Little is known about functional differences amongst RON isoforms RON155, RON160 and RON165. The purpose of this study was to determine the effect of various RON kinase isoforms on cell motility.
  
  
  METHODS
  Cell lines with stable expression of wtRON were generated by inserting the coding region of RON in pTagRFP (tagged red fluorescence protein plasmid). The expression constructs of RON variants (RON155, RON160 and RON165) were generated by creating a mutagenesis-based wtRON-pTag RFP plasmid and stably transfected into HEK 293 cells. The wound closure scratch assay was used to investigate the effect on cell migratory capacity of wild type RON and its variants.
  
  
  RESULTS
  RON transfected cells demonstrated increased cell motility compared to HEK293 control cells. RON165 cell motility was significantly increased compared to RON160 (mean percentage of wound covered 37.37% vs. 32.40%; p = 0.03).
  
  
  CONCLUSIONS
  RON tyrosine kinase isoforms have variable cell motility. This may reflect a difference in the behavior of malignant epithelial cells and their capacity for metastasis.
authors.affiliation: University of New Mexico Health Sciences Center, MSC 10 5610, 1 University of New Mexico, Albuquerque, New Mexico 87131, United States.
authors.forename: Alissa
authors.initials: A
authors.lastname: Greenbaum
authors.affiliation: Division of Surgical Oncology, Department of Surgery, UNM Comprehensive Cancer Center, MSC 07 4025, University of New Mexico, Albuquerque, New Mexico 87131, United States.
authors.forename: Ashwani
authors.initials: A
authors.lastname: Rajput
authors.affiliation: Division of Surgical Oncology, Department of Surgery, MSC 07 4025, University of New Mexico, Albuquerque, New Mexico 87131, United States.
authors.forename: Guanghua
authors.initials: G
authors.lastname: Wan
keywords: Biochemistry; Biological sciences; Cell biology