Expression of RON in colorectal cancer and its relationships with tumor cell behavior and prognosis

Tumori. Sep-Oct 2012;98(5):652-62. doi: 10.1700/1190.13208.

Abstract

Aims and background: The aims of the current study were to evaluate whether recepteur d'origine nantais (RON) affects tumor cell behavior and oncogenic signaling pathways in colorectal cancer, and to examine the relationship of its expression with various clinicopathological parameters and patient survival.

Methods: Immunohistochemistry, Western blot and RT-PCR were used to detect the expression of the RON gene in human colorectal cancer tissue. To study the biological role of RON in tumor cell behavior and cellular signaling pathways, we used small interfering RNA (siRNA) to knock down RON gene expression in human colorectal cancer cell lines.

Results: Knockdown of RON inhibited the induction of the invasive growth phenotype and the activation of oncogenic signaling pathways including Akt, MAPK and β-catenin. RON overexpression was associated with tumor size, lymphovascular invasion, depth of invasion, lymph node metastasis, distant metastasis, tumor stage and poor survival.

Conclusions: These results suggest that RON overexpression may help in predicting poor clinical outcomes in colorectal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Colon / chemistry
  • Colon / metabolism
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lymph Nodes / metabolism*
  • Lymph Nodes / pathology*
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Mitogen-Activated Protein Kinases / metabolism
  • Neoplasm Invasiveness
  • Predictive Value of Tests
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Signal Transduction
  • Up-Regulation
  • beta Catenin / metabolism

Substances

  • beta Catenin
  • RON protein
  • Receptor Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases