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RON kinase isoforms demonstrate variable cell motility in normal cells

Alissa Greenbaum1, Ashwani Rajput2, Guanghua Wan3

  • 1University of New Mexico Health Sciences Center, MSC 10 5610, 1 University of New Mexico, Albuquerque, New Mexico 87131, United States.

Heliyon
|September 23, 2016
PubMed
Abstract

Insights

Aberrant activation of the RON tyrosine kinase promotes cancer metastasis. This study found that different RON isoforms, particularly RON165, significantly increase cancer cell motility, suggesting varied roles in epithelial malignancies.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Aberrant activation of the RON (Recepteur d'Origine Nantais) tyrosine kinase disrupts normal epithelial cell growth pathways, leading to uncontrolled proliferation, enhanced motility, and reduced apoptosis.
  • Wild-type RON is implicated in the metastasis of epithelial cancers, making it a significant therapeutic target for colorectal, breast, gastric, and pancreatic cancers.
  • Functional distinctions among RON isoforms (RON155, RON160, and RON165) remain largely unexplored.

Purpose of the Study:

  • To investigate the functional differences among RON tyrosine kinase isoforms.
  • To determine the specific impact of RON155, RON160, and RON165 on epithelial cell motility.

Main Methods:

  • Stable expression of wild-type RON and its variants (RON155, RON160, RON165) in HEK 293 cells using pTagRFP constructs.
  • Utilizing the wound closure scratch assay to quantitatively assess cell migratory capacity.
  • Comparing the motility of RON-transfected cells against non-transfected HEK293 control cells.

Main Results:

  • RON transfection significantly increased cell motility compared to control HEK293 cells.
  • RON165 isoform demonstrated a statistically significant increase in cell motility compared to the RON160 isoform (37.37% vs. 32.40%, p = 0.03).

Conclusions:

  • RON tyrosine kinase isoforms exhibit differential effects on cell motility.
  • These variations in motility may contribute to distinct behaviors of malignant epithelial cells and influence their metastatic potential.
Keywords:
BiochemistryBiological sciencesCell biology

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