| http://purl.uniprot.org/citations/21619683 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21619683 | http://www.w3.org/2000/01/rdf-schema#comment | "BackgroundEpithelial to mesenchymal transition (EMT) occurs during cancer cell invasion and malignant metastasis. Features of EMT include spindle-like cell morphology, loss of epithelial cellular markers and gain of mesenchymal phenotype. Activation of the RON receptor tyrosine kinase by macrophage-stimulating protein (MSP) has been implicated in cellular EMT program; however, the major signaling determinant(s) responsible for MSP-induced EMT is unknown.ResultsThe study presented here demonstrates that RSK2, a downstream signaling protein of the Ras-Erk1/2 pathway, is the principal molecule that links MSP-activated RON signaling to complete EMT. Using MDCK cells expressing RON as a model, a spindle-shape based screen was conducted, which identifies RSK2 among various intracellular proteins as a potential signaling molecule responsible for MSP-induced EMT. MSP stimulation dissociated RSK2 with Erk1/2 and promoted RSK2 nuclear translocation. MSP strongly induced RSK2 phosphorylation in a dose-dependent manner. These effects relied on RON and Erk1/2 phosphorylation, which is significantly potentiated by transforming growth factor (TGF)-β1, an EMT-inducing cytokine. Specific RSK inhibitor SL0101 completely prevented MSP-induced RSK phosphorylation, which results in inhibition of MSP-induced spindle-like morphology and suppression of cell migration associated with EMT. In HT-29 cancer cells that barely express RSK2, forced RSK2 expression results in EMT-like phenotype upon MSP stimulation. Moreover, specific siRNA-mediated silencing of RSK2 but not RSK1 in L3.6pl pancreatic cancer cells significantly inhibited MSP-induced EMT-like phenotype and cell migration.ConclusionsMSP-induced RSK2 activation is a critical determinant linking RON signaling to cellular EMT program. Inhibition of RSK2 activity may provide a therapeutic opportunity for blocking RON-mediated cancer cell migration and subsequent invasion."xsd:string |
| http://purl.uniprot.org/citations/21619683 | http://purl.org/dc/terms/identifier | "doi:10.1186/1476-4598-10-66"xsd:string |
| http://purl.uniprot.org/citations/21619683 | http://purl.uniprot.org/core/author | "Ma Q."xsd:string |
| http://purl.uniprot.org/citations/21619683 | http://purl.uniprot.org/core/author | "Zhou Y.Q."xsd:string |
| http://purl.uniprot.org/citations/21619683 | http://purl.uniprot.org/core/author | "Zhang R.W."xsd:string |
| http://purl.uniprot.org/citations/21619683 | http://purl.uniprot.org/core/author | "Wang M.H."xsd:string |
| http://purl.uniprot.org/citations/21619683 | http://purl.uniprot.org/core/author | "Guin S."xsd:string |
| http://purl.uniprot.org/citations/21619683 | http://purl.uniprot.org/core/author | "Padhye S.S."xsd:string |
| http://purl.uniprot.org/citations/21619683 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21619683 | http://purl.uniprot.org/core/name | "Mol Cancer"xsd:string |
| http://purl.uniprot.org/citations/21619683 | http://purl.uniprot.org/core/pages | "66"xsd:string |
| http://purl.uniprot.org/citations/21619683 | http://purl.uniprot.org/core/title | "Ribosomal protein S6 kinase (RSK)-2 as a central effector molecule in RON receptor tyrosine kinase mediated epithelial to mesenchymal transition induced by macrophage-stimulating protein."xsd:string |
| http://purl.uniprot.org/citations/21619683 | http://purl.uniprot.org/core/volume | "10"xsd:string |
| http://purl.uniprot.org/citations/21619683 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/21619683 |
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| http://purl.uniprot.org/uniprot/#_B1AXG1-mappedCitation-21619683 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21619683 |
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