| http://purl.uniprot.org/citations/29046336 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/29046336 | http://www.w3.org/2000/01/rdf-schema#comment | "Protein phosphatase 2A (PP2A) complexes counteract many oncogenic kinase pathways. In cancer cells, PP2A function can be compromised by several mechanisms, including sporadic mutations in its scaffolding A and regulatory B subunits or more frequently through overexpression of cellular PP2A inhibitors. Here, we identify a novel genetic mechanism by which PP2A function is recurrently affected in human cancer, involving haploinsufficiency of PPP2R4, a gene encoding the cellular PP2A activator PTPA. Notably, up to 70% of cancer patients showed a heterozygous deletion or missense mutations in PPP2R4 Cancer-associated PTPA mutants exhibited decreased abilities to bind the PP2A-C subunit or activate PP2A and failed to reverse the tumorigenic phenotype induced by PTPA suppression, indicating they function as null alleles. In Ppp2r4 gene-trapped (gt) mice showing residual PTPA expression, total PP2A activity and methylation were reduced, selectively affecting specific PP2A holoenzymes. Both PTPAgt/gt and PTPA+/gt mice showed higher rates of spontaneous tumors, mainly hematologic malignancies and hepatocellular adenomas and carcinomas. These tumors exhibited increased c-Myc phosphorylation and increased Wnt or Hedgehog signaling. We observed a significant reduction in lifespan in PTPA+/gt mice compared with wild-type mice. In addition, chemical-induced skin carcinogenesis was accelerated in PTPA+/gt compared with wild-type mice. Our results provide evidence for PPP2R4 as a haploinsufficient tumor suppressor gene, defining a high-penetrance genetic mechanism for PP2A inhibition in human cancer. Cancer Res; 77(24); 6825-37. ©2017 AACR."xsd:string |
| http://purl.uniprot.org/citations/29046336 | http://purl.org/dc/terms/identifier | "doi:10.1158/0008-5472.can-16-2911"xsd:string |
| http://purl.uniprot.org/citations/29046336 | http://purl.uniprot.org/core/author | "Haesen D."xsd:string |
| http://purl.uniprot.org/citations/29046336 | http://purl.uniprot.org/core/author | "Janssens V."xsd:string |
| http://purl.uniprot.org/citations/29046336 | http://purl.uniprot.org/core/author | "Westermarck J."xsd:string |
| http://purl.uniprot.org/citations/29046336 | http://purl.uniprot.org/core/author | "Carmeliet P."xsd:string |
| http://purl.uniprot.org/citations/29046336 | http://purl.uniprot.org/core/author | "Dewerchin M."xsd:string |
| http://purl.uniprot.org/citations/29046336 | http://purl.uniprot.org/core/author | "Radaelli E."xsd:string |
| http://purl.uniprot.org/citations/29046336 | http://purl.uniprot.org/core/author | "Kalev P."xsd:string |
| http://purl.uniprot.org/citations/29046336 | http://purl.uniprot.org/core/author | "Lambrecht C."xsd:string |
| http://purl.uniprot.org/citations/29046336 | http://purl.uniprot.org/core/author | "Sagaert X."xsd:string |
| http://purl.uniprot.org/citations/29046336 | http://purl.uniprot.org/core/author | "Sents W."xsd:string |
| http://purl.uniprot.org/citations/29046336 | http://purl.uniprot.org/core/author | "Sablina A."xsd:string |
| http://purl.uniprot.org/citations/29046336 | http://purl.uniprot.org/core/author | "Meeusen B."xsd:string |
| http://purl.uniprot.org/citations/29046336 | http://purl.uniprot.org/core/author | "Miermans E."xsd:string |
| http://purl.uniprot.org/citations/29046336 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/29046336 | http://purl.uniprot.org/core/name | "Cancer Res"xsd:string |
| http://purl.uniprot.org/citations/29046336 | http://purl.uniprot.org/core/pages | "6825-6837"xsd:string |
| http://purl.uniprot.org/citations/29046336 | http://purl.uniprot.org/core/title | "PP2A Inactivation Mediated by PPP2R4 Haploinsufficiency Promotes Cancer Development."xsd:string |
| http://purl.uniprot.org/citations/29046336 | http://purl.uniprot.org/core/volume | "77"xsd:string |
| http://purl.uniprot.org/citations/29046336 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/29046336 |
| http://purl.uniprot.org/citations/29046336 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/29046336 |
| http://purl.uniprot.org/uniprot/#_D3Z783-mappedCitation-29046336 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29046336 |
| http://purl.uniprot.org/uniprot/#_D3Z7S6-mappedCitation-29046336 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29046336 |