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Identification and Characterization of Metastatic Factors by Gene Transfer into the Novel RIP-Tag; RIP-tva Murine Model
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The RON-receptor regulates pancreatic cancer cell migration through phosphorylation-dependent breakdown of the

Peter T Yu1, Michele Babicky, Dawn Jaquish

  • 1Department of Surgery, Division of Surgical Oncology, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.

International Journal of Cancer
|January 26, 2012
PubMed

Insights

Researchers discovered that the receptor tyrosine kinase RON interacts with plectin and integrin-β4 (ITGB4) in pancreatic cancer cells. This interaction disrupts cell anchoring, promoting invasive growth and migration, suggesting new therapeutic targets.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Receptor tyrosine kinase (RON) is overexpressed in pancreatic cancer, driving invasive growth.
  • Mechanisms of RON-mediated phenotypes in pancreatic cancer are not well understood.
  • Plectin and integrin-β4 (ITGB4) are implicated in cell adhesion and signaling.

Purpose of the Study:

  • To identify novel interactants of RON in pancreatic cancer cells.
  • To elucidate the role of RON-plectin-ITGB4 interactions in pancreatic cancer cell migration.
  • To investigate the signaling pathways involved in RON-mediated cell migration.

Main Methods:

  • Multidimensional protein identification analysis to find RON interactants.
  • Co-immunoprecipitation assays to confirm protein interactions.
  • Small hairpin ribosomal nucleic acid (shRNA) to suppress plectin expression.
  • Pharmacological inhibition of phosphoinositide-3 (PI3) kinase and mitogen-activated protein kinase (MEK).

Main Results:

  • Plectin was identified as a novel interactant of RON.
  • RON activation by macrophage-stimulating protein disrupts the plectin-ITGB4 complex.
  • Suppression of plectin expression phenocopies RON-induced cell migration.
  • Disruption of the plectin-ITGB4 interaction is dependent on RON and PI3 kinase activity.

Conclusions:

  • Plectin and ITGB4 form hemidesmosomes that anchor pancreatic cancer cells and inhibit migration.
  • RON signaling disrupts plectin-ITGB4 interactions, promoting cell migration.
  • This study defines a novel RON-plectin interaction and its role in pancreatic cancer invasion.
  • Targeting RON kinase activity may offer a therapeutic strategy for pancreatic cancer.

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