IGF1-R signals through the RON receptor to mediate pancreatic cancer cell migration

Dawn V Jaquish1, Peter T Yu, David J Shields

  • 1Department of Surgery, Division of Surgical Oncology, Moores Cancer Center, University of California, 3855 Health Sciences Drive, San Diego, CA 92093-0987, USA.

Carcinogenesis
|May 14, 2011
PubMed

Insights

Pancreatic cancer cells utilize the RON receptor tyrosine kinase (RTK) to mediate migration in response to insulin-like growth factor 1 (IGF-1). This study reveals a novel interaction between RON and IGF-1R, highlighting RON

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • The receptor tyrosine kinase (RTK) RON is overexpressed in most pancreatic cancers, but its function is unclear.
  • Previous research linked RON to resistance against insulin-like growth factor receptor (IGF1-R) therapies in childhood sarcoma.

Purpose of the Study:

  • To investigate the role of RON in pancreatic cancer cell biology.
  • To identify novel proteins interacting with RON in pancreatic cancer cells.

Main Methods:

  • Multidimensional protein identification analysis to find RON interactants.
  • Confirmation of IGF-1R interaction with RON in pancreatic cancer cell lines.
  • Scratch assays to assess cell migration and RON-dependent signaling.

Main Results:

  • Insulin-like growth factor 1 (IGF-1) was identified as an interacting partner of RON.
  • IGF-1 rapidly phosphorylates RON, but signaling is unidirectional (RON does not activate IGF-1R).
  • IGF-1-induced pancreatic cancer cell migration is dependent on RON signaling, involving STAT-3 activation.

Conclusions:

  • A novel interaction between RON and IGF-1R is defined in pancreatic cancer.
  • RON acts as a key mediator of IGF-1R signaling, consistent across epithelial and mesenchymal cancers.
  • Further research is needed to explore RON's role in therapeutic resistance and identify biomarkers.

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