| http://purl.uniprot.org/citations/29941929 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/29941929 | http://www.w3.org/2000/01/rdf-schema#comment | "G protein αs (GNAS) mediates receptor-stimulated cAMP signalling, which integrates diverse environmental cues with intracellular responses. GNAS is mutationally activated in multiple tumour types, although its oncogenic mechanisms remain elusive. We explored this question in pancreatic tumourigenesis where concurrent GNAS and KRAS mutations characterize pancreatic ductal adenocarcinomas (PDAs) arising from intraductal papillary mucinous neoplasms (IPMNs). By developing genetically engineered mouse models, we show that GnasR201C cooperates with KrasG12D to promote initiation of IPMN, which progress to invasive PDA following Tp53 loss. Mutant Gnas remains critical for tumour maintenance in vivo. This is driven by protein-kinase-A-mediated suppression of salt-inducible kinases (Sik1-3), associated with induction of lipid remodelling and fatty acid oxidation. Comparison of Kras-mutant pancreatic cancer cells with and without Gnas mutations reveals striking differences in the functions of this network. Thus, we uncover Gnas-driven oncogenic mechanisms, identify Siks as potent tumour suppressors, and demonstrate unanticipated metabolic heterogeneity among Kras-mutant pancreatic neoplasms."xsd:string |
| http://purl.uniprot.org/citations/29941929 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41556-018-0122-3"xsd:string |
| http://purl.uniprot.org/citations/29941929 | http://purl.uniprot.org/core/author | "Kato Y."xsd:string |
| http://purl.uniprot.org/citations/29941929 | http://purl.uniprot.org/core/author | "Haas W."xsd:string |
| http://purl.uniprot.org/citations/29941929 | http://purl.uniprot.org/core/author | "Mizukami Y."xsd:string |
| http://purl.uniprot.org/citations/29941929 | http://purl.uniprot.org/core/author | "Sakamoto K."xsd:string |
| http://purl.uniprot.org/citations/29941929 | http://purl.uniprot.org/core/author | "Screaton R.A."xsd:string |
| http://purl.uniprot.org/citations/29941929 | http://purl.uniprot.org/core/author | "Bardeesy N."xsd:string |
| http://purl.uniprot.org/citations/29941929 | http://purl.uniprot.org/core/author | "Grossman E.A."xsd:string |
| http://purl.uniprot.org/citations/29941929 | http://purl.uniprot.org/core/author | "Nomura D.K."xsd:string |
| http://purl.uniprot.org/citations/29941929 | http://purl.uniprot.org/core/author | "Ryan D.P."xsd:string |
| http://purl.uniprot.org/citations/29941929 | http://purl.uniprot.org/core/author | "Sadreyev R.I."xsd:string |
| http://purl.uniprot.org/citations/29941929 | http://purl.uniprot.org/core/author | "Ji F."xsd:string |
| http://purl.uniprot.org/citations/29941929 | http://purl.uniprot.org/core/author | "Boukhali M."xsd:string |
| http://purl.uniprot.org/citations/29941929 | http://purl.uniprot.org/core/author | "Mino-Kenudson M."xsd:string |
| http://purl.uniprot.org/citations/29941929 | http://purl.uniprot.org/core/author | "Liss A.S."xsd:string |
| http://purl.uniprot.org/citations/29941929 | http://purl.uniprot.org/core/author | "Patra K.C."xsd:string |
| http://purl.uniprot.org/citations/29941929 | http://purl.uniprot.org/core/author | "Castillo C.F."xsd:string |
| http://purl.uniprot.org/citations/29941929 | http://purl.uniprot.org/core/author | "Revenco I."xsd:string |
| http://purl.uniprot.org/citations/29941929 | http://purl.uniprot.org/core/author | "Widholz S."xsd:string |
| http://purl.uniprot.org/citations/29941929 | http://purl.uniprot.org/core/date | "2018"xsd:gYear |
| http://purl.uniprot.org/citations/29941929 | http://purl.uniprot.org/core/name | "Nat Cell Biol"xsd:string |
| http://purl.uniprot.org/citations/29941929 | http://purl.uniprot.org/core/pages | "811-822"xsd:string |
| http://purl.uniprot.org/citations/29941929 | http://purl.uniprot.org/core/title | "Mutant GNAS drives pancreatic tumourigenesis by inducing PKA-mediated SIK suppression and reprogramming lipid metabolism."xsd:string |