Abstract:
:The RON receptor tyrosine kinase and its ligand macrophage stimulating protein (MSP) play a role in epithelial tumorigenesis. We report here a novel RON variant that antagonizes the RON-MSP pathway in various cancer cells. The variant is an 85 kDa soluble protein from an mRNA transcript with an insertion of 49 nucleotides between exons 5 and 6. The insertion created a stop codon leading to the formation of a RON variant consisting of the entire 35 kDa alpha-chain and a 45 kDa partial extracellular beta-chain. The protein was featured by a sema domain, a hinge motif and a portion of the first IPT unit (designated as RONDelta85). RONDelta85 binds directly to MSP, forms MSP-RONDelta85 complex, and inhibits RON phosphorylation. RONDelta85 disrupts RON or RONDelta160 dimerization, prevents their phosphorylation, and attenuates downstream signaling events. The action of RONDelta85 is specific to RON and has no effect on MET and EGFR. In colon and pancreatic cancer cells, RONDelta85 inhibits spontaneous or MSP-induced Erk1/2 and AKT phosphorylation, which results in impaired cell proliferation and colony formation. RONDelta85 also inhibits spontaneous and MSP-induced cell migration. We conclude that RONDelta85 is an antagonist to the MSP-RON pathway, which has potential for regulating RON/RON160-mediated tumorigenic activities.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
Ma Q,Zhang K,Yao HP,Zhou YQ,Padhye S,Wang MHdoi
10.3892/ijo_00000642subject
Has Abstractpub_date
2010-06-01 00:00:00pages
1551-61issue
6eissn
1019-6439issn
1791-2423journal_volume
36pub_type
杂志文章abstract::Human chorionic gonadotropin (hCG) inhibits the growth of human breast epithelial cells MCF-7. Differential display was utilized for analyzing RNA of hCG-treated MCF-7 cells in order to determine whether this effect was mediated by specific gene activation or repression. Three cDNA clones, 19, 29 and 44, were differen...
journal_title:International journal of oncology
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journal_title:International journal of oncology
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journal_title:International journal of oncology
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journal_title:International journal of oncology
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journal_title:International journal of oncology
pub_type: 杂志文章,评审
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journal_title:International journal of oncology
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journal_title:International journal of oncology
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journal_title:International journal of oncology
pub_type: 杂志文章,评审
doi:
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更新日期:2003-06-01 00:00:00
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journal_title:International journal of oncology
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更新日期:2006-09-01 00:00:00
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journal_title:International journal of oncology
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更新日期:2006-11-01 00:00:00
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