Related Experiment Video

Updated: Jul 16, 2026

Oncogene Expression Analysis with Alterations in pH in a Pancreatic Ductal Cell Line
06:24

Oncogene Expression Analysis with Alterations in pH in a Pancreatic Ductal Cell Line

Published on: April 11, 2025

Tyrosine kinase receptor RON in human pancreatic cancer: expression, function, and validation as a target

E Ramsay Camp1, Anthony Yang, Mike J Gray

  • 1Department of Surgical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.

Cancer
|February 22, 2007
PubMed
Abstract

Insights

RON receptor tyrosine kinase is overexpressed in pancreatic cancer, driving tumor growth and metastasis. Inhibiting RON with a monoclonal antibody significantly reduced tumor progression in preclinical models, suggesting a new therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Tyrosine kinase receptors like c-MET drive epithelial-mesenchymal transition (EMT), increasing cancer cell motility.
  • The related receptor tyrosine kinase RON was investigated for its role in pancreatic cancer.

Purpose of the Study:

  • To determine if RON is expressed in human pancreatic cancer.
  • To investigate if RON activation induces EMT and promotes pancreatic cancer progression.
  • To evaluate RON as a therapeutic target in a preclinical pancreatic cancer model.

Main Methods:

  • Immunohistochemistry, RT-PCR, and Western blot were used to assess RON expression in patient samples and cell lines.
  • Pancreatic cancer cells were treated with macrophage stimulating protein (MSP), the RON ligand, to study cell migration, invasion, and EMT markers.
  • A RON monoclonal antibody (MoAb) was employed to block RON activation and assess its effects on signaling, cell behavior, and tumor growth in vivo.

Main Results:

  • RON was overexpressed in 93% of pancreatic cancer specimens and present in all tested cell lines.
  • MSP-induced RON activation increased cell migration, invasion, and EMT markers (decreased E-cadherin, increased nuclear beta-catenin).
  • RON inhibition by MoAb suppressed downstream signaling, cell migration, invasion, and significantly reduced tumor growth in mouse models (approx. 60% inhibition).

Conclusions:

  • RON activation promotes pancreatic cancer progression through EMT.
  • Inhibiting RON signaling offers a promising therapeutic strategy to impede pancreatic tumor growth and metastasis.
  • Targeting RON may represent a novel approach for pancreatic cancer treatment.

More Related Videos

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays07:42

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays

Published on: September 19, 2018

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include: