| http://purl.uniprot.org/citations/22988093 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22988093 | http://www.w3.org/2000/01/rdf-schema#comment | "K-RAS-activating mutations occur frequently in non-small cell lung cancer, leading to aberrant activation of the Ras-MAPK signaling pathway that contributes to the malignant phenotype. However, the development of Ras-targeted therapeutics remains challenging. Here, we show that MED23, a component of the multisubunit Mediator complex that is known to integrate signaling and gene activities, is selectively important for Ras-active lung cancer. By screening a large panel of human lung cancer cell lines with or without a Ras mutation, we found that Med23 RNAi specifically inhibits the proliferation and tumorigenicity of lung cancer cells with hyperactive Ras activity. Med23 deficiency in fibroblasts selectively inhibited the oncogenic transformation induced by Ras but not by c-Myc. The transcription factor ELK1, which is phosphorylated by MAPK for relaying Ras signaling to MED23, also was required for the Ras-driven oncogenesis. Transcriptome analysis revealed that MED23 and ELK1 co-regulate a common set of target genes enriched in regulating cell-cycle and -proliferation functions to support the Ras dependency. Furthermore, MED23 was up-regulated by Ras transformation in correlation with the strength of Ras signaling as indicated by the ELK1 phosphorylation level and was found to be overexpressed in both Ras-mutated lung cancer cell lines and primary tumor samples. Remarkably, lower Med23 expression predicted better survival in Ras-active lung cancer patients and xenograft mice. Collectively, our findings demonstrate a critical role for MED23 in enabling the "Ras-addiction" of lung carcinogenesis, thus providing a vulnerable target for the treatment of Ras-active lung cancer."xsd:string |
| http://purl.uniprot.org/citations/22988093 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1204311109"xsd:string |
| http://purl.uniprot.org/citations/22988093 | http://purl.uniprot.org/core/author | "Liu Y."xsd:string |
| http://purl.uniprot.org/citations/22988093 | http://purl.uniprot.org/core/author | "Wang G."xsd:string |
| http://purl.uniprot.org/citations/22988093 | http://purl.uniprot.org/core/author | "Yang X."xsd:string |
| http://purl.uniprot.org/citations/22988093 | http://purl.uniprot.org/core/author | "Zhao M."xsd:string |
| http://purl.uniprot.org/citations/22988093 | http://purl.uniprot.org/core/author | "Yan J."xsd:string |
| http://purl.uniprot.org/citations/22988093 | http://purl.uniprot.org/core/author | "Xia M."xsd:string |
| http://purl.uniprot.org/citations/22988093 | http://purl.uniprot.org/core/author | "Ji H."xsd:string |
| http://purl.uniprot.org/citations/22988093 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22988093 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/22988093 | http://purl.uniprot.org/core/pages | "E2813-22"xsd:string |
| http://purl.uniprot.org/citations/22988093 | http://purl.uniprot.org/core/title | "Selective requirement for Mediator MED23 in Ras-active lung cancer."xsd:string |
| http://purl.uniprot.org/citations/22988093 | http://purl.uniprot.org/core/volume | "109"xsd:string |
| http://purl.uniprot.org/citations/22988093 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/22988093 |
| http://purl.uniprot.org/citations/22988093 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/22988093 |
| http://purl.uniprot.org/uniprot/#_A0A221ZRZ1-mappedCitation-22988093 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22988093 |
| http://purl.uniprot.org/uniprot/#_Q0VDV7-mappedCitation-22988093 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22988093 |
| http://purl.uniprot.org/uniprot/#_A0A5P8I3H7-mappedCitation-22988093 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22988093 |
| http://purl.uniprot.org/uniprot/#_A0A221ZRZ4-mappedCitation-22988093 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22988093 |
| http://purl.uniprot.org/uniprot/#_A0A221ZRZ5-mappedCitation-22988093 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22988093 |
| http://purl.uniprot.org/uniprot/#_A5HC25-mappedCitation-22988093 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22988093 |
| http://purl.uniprot.org/uniprot/#_F8WJB0-mappedCitation-22988093 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22988093 |
| http://purl.uniprot.org/uniprot/#_A5HC02-mappedCitation-22988093 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22988093 |