Chonnam Med J.  2017 Sep;53(3):178-186. 10.4068/cmj.2017.53.3.178.

Role of Recepteur D'origine Nantais on Gastric Cancer Development and Progression

• Yang SY
• Nguyen TT
• Ung TT
• Jung YD

• KMID: 2390431
• DOI: http://doi.org/10.4068/cmj.2017.53.3.178

Abstract

Recepteur d'origine nantais (RON) is a receptor tyrosine kinase belonging to the subfamily of which c-MET is the prototype. Large epidemiologic studies have confirmed the strong association between RON and gastric cancer development. Constitutive activation of RON signaling directly correlates with tumorigenic phenotypes of gastric cancer and a poor survival rate in advanced gastric cancer patients. In this review, we focus on recent evidence of the aberrant expression and activation of RON in gastric cancer tumors and provide insights into the mechanism of RON signaling associated with gastric cancer progression and metastasis. Current therapeutics against RON in gastric cancer are summarized.

Keyword

Humans; Stomach Neoplasms; MET protein, human; Proto-Oncogene Proteins c-met; Phenotype

MeSH Terms

Epidemiologic Studies
Humans
Neoplasm Metastasis
Phenotype
Protein-Tyrosine Kinases
Proto-Oncogene Proteins c-met
Stomach Neoplasms*
Survival Rate
Protein-Tyrosine Kinases
Proto-Oncogene Proteins c-met

Figure

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  FIG. 1 Comparison of human RON and c-MET. Sema: semaphoring, PSI: plexin semaphorin-integrin, IPT: immunoglobulin-plexin-transcription factor, TM: transmembrane, TK: tyrosine kinase catalytic sites.

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  FIG. 2 Alternative splicing and various isoforms of RON. E: Exon.

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  FIG. 3 Receptor activation of RON. SOS: son of sevenless, GRB2: growth factor receptor-bound protein 2, CBL: casitas B-lineage lymphome.

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  FIG. 4 Downstream signaling of RON activation. GRB2: growth factor receptor-bound protein 2, MAPK: mitogen-activated protein kinases, ERK1/2: extracellular signal-regulated kinase 1/2, IκBα: nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha, EMT: epithelial mesenchymal transition, TGF-β: transforming growth factor beta, NF-κB: nuclear factor kappa light chain enhancer of activated B cells, JAK: janus kinase, STAT3: signal transducer and activator of transcription 3, mTOR: mamalian target of rapamycin, HIF1α: hypoxia inducible factor 1-alplha, P70S6K: ribosomal protein S6 kinase, GSK3β: Glycogen synthase kinase 3 beta.

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  FIG. 5 Intracellular signals of RON activation for the growth and invasion in gastric cancer cells. CDKI: Cycline-dependent kinase inhibitor, CDK4: Cycline-dependent kinase 4, MAPK: Mitogen-activated protein kinases, Erk1/2: extracellular signal-regulated kinase 1/2, JNK: c-Jun N-terminal kinases, AP-1: Activator protein-1, NF-kB: nuclear factor kappa-light-chain-enhancer of activated B cells, UPAR: Urokinase receptor.

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  FIG. 6 Intracellular signals of RON activation for the cell apoptosis in gastric cancer cells. XIAP: X-linked inhibitor of apoptosis protein, Bcl-2: B-cell lymphoma 2, Bax: Bcl-2-associated X protein, Bik: BCL2 Interacting Killer, Bad: Bcl-2-associated death promoter, Bid: BH3 interacting domain death agonist, BimSL: Bcl-2-like protein 11, PTEN: Phosphatase and tensin homolog.

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