| http://purl.uniprot.org/citations/31086176 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/31086176 | http://www.w3.org/2000/01/rdf-schema#comment | "Trastuzumab is integral to HER2+ cancer treatment, but its therapeutic index is narrowed by the development of resistance. Phosphorylation of the translation initiation factor eIF2α (eIF2α-P) is the nodal point of the integrated stress response, which promotes survival or death in a context-dependent manner. Here, we show an anti-tumor function of the protein kinase PKR and its substrate eIF2α in a mouse HER2+ breast cancer model. The anti-tumor function depends on the transcription factor ATF4, which upregulates the CDK inhibitor P21CIP1 and activates JNK1/2. The PKR/eIF2α-P arm is induced by Trastuzumab in sensitive but not resistant HER2+ breast tumors. Also, eIF2α-P stimulation by the phosphatase inhibitor SAL003 substantially increases Trastuzumab potency in resistant HER2+ breast and gastric tumors. Increased eIF2α-P prognosticates a better response of HER2+ metastatic breast cancer patients to Trastuzumab therapy. Hence, the PKR/eIF2α-P arm antagonizes HER2 tumorigenesis whereas its pharmacological stimulation improves the efficacy of Trastuzumab therapy."xsd:string |
| http://purl.uniprot.org/citations/31086176 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41467-019-10138-8"xsd:string |
| http://purl.uniprot.org/citations/31086176 | http://purl.uniprot.org/core/author | "Wang S."xsd:string |
| http://purl.uniprot.org/citations/31086176 | http://purl.uniprot.org/core/author | "Torres J."xsd:string |
| http://purl.uniprot.org/citations/31086176 | http://purl.uniprot.org/core/author | "Koromilas A.E."xsd:string |
| http://purl.uniprot.org/citations/31086176 | http://purl.uniprot.org/core/author | "Basik M."xsd:string |
| http://purl.uniprot.org/citations/31086176 | http://purl.uniprot.org/core/author | "Assaker G."xsd:string |
| http://purl.uniprot.org/citations/31086176 | http://purl.uniprot.org/core/author | "Deschenes J."xsd:string |
| http://purl.uniprot.org/citations/31086176 | http://purl.uniprot.org/core/author | "Abdulkarim B."xsd:string |
| http://purl.uniprot.org/citations/31086176 | http://purl.uniprot.org/core/author | "Chabot C."xsd:string |
| http://purl.uniprot.org/citations/31086176 | http://purl.uniprot.org/core/author | "Sabri S."xsd:string |
| http://purl.uniprot.org/citations/31086176 | http://purl.uniprot.org/core/author | "Ursini-Siegel J."xsd:string |
| http://purl.uniprot.org/citations/31086176 | http://purl.uniprot.org/core/author | "Buchanan M."xsd:string |
| http://purl.uniprot.org/citations/31086176 | http://purl.uniprot.org/core/author | "Krishnamoorthy J."xsd:string |
| http://purl.uniprot.org/citations/31086176 | http://purl.uniprot.org/core/author | "Aguilar-Mahecha A."xsd:string |
| http://purl.uniprot.org/citations/31086176 | http://purl.uniprot.org/core/author | "Darini C."xsd:string |
| http://purl.uniprot.org/citations/31086176 | http://purl.uniprot.org/core/author | "Ghaddar N."xsd:string |
| http://purl.uniprot.org/citations/31086176 | http://purl.uniprot.org/core/date | "2019"xsd:gYear |
| http://purl.uniprot.org/citations/31086176 | http://purl.uniprot.org/core/name | "Nat Commun"xsd:string |
| http://purl.uniprot.org/citations/31086176 | http://purl.uniprot.org/core/pages | "2139"xsd:string |
| http://purl.uniprot.org/citations/31086176 | http://purl.uniprot.org/core/title | "An integrated stress response via PKR suppresses HER2+ cancers and improves trastuzumab therapy."xsd:string |
| http://purl.uniprot.org/citations/31086176 | http://purl.uniprot.org/core/volume | "10"xsd:string |
| http://purl.uniprot.org/citations/31086176 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/31086176 |
| http://purl.uniprot.org/citations/31086176 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/31086176 |