| http://purl.uniprot.org/citations/29717265 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/29717265 | http://www.w3.org/2000/01/rdf-schema#comment | "Poor oxygenation is a common hallmark of solid cancers that strongly associates with aggressive tumor progression and treatment resistance. While a hypoxia-inducible factor 1α (HIF-1α)-associated transcriptional overexpression of the hepatocyte growth factor (HGF) receptor tyrosine kinase (RTK) MET has been previously documented, any regulation of the HIF-1α system through MET downstream signaling in hypoxic tumors has not been yet described. By using MET-driven in vitro as well as ex vivo tumor organotypic fresh tissue models we report that MET targeting results in depletion of HIF-1α and its various downstream targets. Mechanistically, we provide evidence that MET regulates HIF-1α levels through a protein translation mechanism that relies on phosphorylation modulation of the eukaryotic initiation factor 4G1 (eIF4G1) on serine 1232 (Ser-1232). Targeted phosphoproteomics data demonstrate a significant drop in eIF4G1 Ser-1232 phosphorylation following MET targeting, which is linked to an increased affinity between eIF4G1 and eIF4E. Since phosphorylation of eIF4G1 on Ser-1232 is largely mediated through mitogen-activated protein kinase (MAPK), we show that expression of a constitutively active K-RAS variant is sufficient to abrogate the inhibitory effect of MET targeting on the HIF-1α pathway with subsequent resistance of tumor cells to MET targeting under hypoxic conditions. Analysis of The Cancer Genome Atlas data demonstrates frequent co-expression of MET, HIF-1α and eIF4G1 in various solid tumors and its impact on disease-free survival of non-small cell lung cancer patients. Clinical relevance of the MET-eIF4G1-HIF-1α pathway is further supported by a co-occurrence of their expression in common tumor regions of individual lung cancer patients."xsd:string |
| http://purl.uniprot.org/citations/29717265 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41388-018-0256-6"xsd:string |
| http://purl.uniprot.org/citations/29717265 | http://purl.uniprot.org/core/author | "Bubendorf L."xsd:string |
| http://purl.uniprot.org/citations/29717265 | http://purl.uniprot.org/core/author | "Blaukat A."xsd:string |
| http://purl.uniprot.org/citations/29717265 | http://purl.uniprot.org/core/author | "Leiser D."xsd:string |
| http://purl.uniprot.org/citations/29717265 | http://purl.uniprot.org/core/author | "Berezowska S."xsd:string |
| http://purl.uniprot.org/citations/29717265 | http://purl.uniprot.org/core/author | "Zimmer Y."xsd:string |
| http://purl.uniprot.org/citations/29717265 | http://purl.uniprot.org/core/author | "Aebersold D.M."xsd:string |
| http://purl.uniprot.org/citations/29717265 | http://purl.uniprot.org/core/author | "Orlando E."xsd:string |
| http://purl.uniprot.org/citations/29717265 | http://purl.uniprot.org/core/author | "Medova M."xsd:string |
| http://purl.uniprot.org/citations/29717265 | http://purl.uniprot.org/core/author | "Gluck A.A."xsd:string |
| http://purl.uniprot.org/citations/29717265 | http://purl.uniprot.org/core/author | "Quintin A."xsd:string |
| http://purl.uniprot.org/citations/29717265 | http://purl.uniprot.org/core/author | "Nisa L."xsd:string |
| http://purl.uniprot.org/citations/29717265 | http://purl.uniprot.org/core/author | "Stroka D.M."xsd:string |
| http://purl.uniprot.org/citations/29717265 | http://purl.uniprot.org/core/author | "Poliakova M."xsd:string |
| http://purl.uniprot.org/citations/29717265 | http://purl.uniprot.org/core/author | "Gavini J."xsd:string |
| http://purl.uniprot.org/citations/29717265 | http://purl.uniprot.org/core/date | "2018"xsd:gYear |
| http://purl.uniprot.org/citations/29717265 | http://purl.uniprot.org/core/name | "Oncogene"xsd:string |
| http://purl.uniprot.org/citations/29717265 | http://purl.uniprot.org/core/pages | "4181-4196"xsd:string |
| http://purl.uniprot.org/citations/29717265 | http://purl.uniprot.org/core/title | "Identification of a MET-eIF4G1 translational regulation axis that controls HIF-1alpha levels under hypoxia."xsd:string |
| http://purl.uniprot.org/citations/29717265 | http://purl.uniprot.org/core/volume | "37"xsd:string |
| http://purl.uniprot.org/citations/29717265 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/29717265 |
| http://purl.uniprot.org/citations/29717265 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/29717265 |
| http://purl.uniprot.org/uniprot/#_D0VY79-mappedCitation-29717265 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29717265 |