| http://purl.uniprot.org/citations/25466250 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25466250 | http://www.w3.org/2000/01/rdf-schema#comment | "Hypermethylation-mediated tumor suppressor gene (TSG) silencing is a central epigenetic alteration in RAS-dependent tumorigenesis. Ten-eleven translocation (TET) enzymes can depress DNA methylation by hydroxylation of 5-methylcytosine (5mC) bases to 5-hydroxymethylcytosine (5hmC). Here, we report that suppression of TET1 is required for KRAS-induced DNA hypermethylation and cellular transformation. In distinct nonmalignant cell lines, oncogenic KRAS promotes transformation by inhibiting TET1 expression via the ERK-signaling pathway. This reduces chromatin occupancy of TET1 at TSG promoters, lowers levels of 5hmC, and increases levels of 5mC and 5mC-dependent transcriptional silencing. Restoration of TET1 expression by ERK pathway inhibition or ectopic TET1 reintroduction in KRAS-transformed cells reactivates TSGs and inhibits colony formation. KRAS knockdown increases TET1 expression and diminishes colony-forming ability, whereas KRAS/TET1 double knockdown bypasses the KRAS dependence of KRAS-addicted cancer cells. Thus, suppression of TET1-dependent DNA demethylation is critical for KRAS-mediated transformation."xsd:string |
| http://purl.uniprot.org/citations/25466250 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.celrep.2014.10.063"xsd:string |
| http://purl.uniprot.org/citations/25466250 | http://purl.uniprot.org/core/author | "Brenner C."xsd:string |
| http://purl.uniprot.org/citations/25466250 | http://purl.uniprot.org/core/author | "Wu B.K."xsd:string |
| http://purl.uniprot.org/citations/25466250 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/25466250 | http://purl.uniprot.org/core/name | "Cell Rep"xsd:string |
| http://purl.uniprot.org/citations/25466250 | http://purl.uniprot.org/core/pages | "1827-1840"xsd:string |
| http://purl.uniprot.org/citations/25466250 | http://purl.uniprot.org/core/title | "Suppression of TET1-dependent DNA demethylation is essential for KRAS-mediated transformation."xsd:string |
| http://purl.uniprot.org/citations/25466250 | http://purl.uniprot.org/core/volume | "9"xsd:string |
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