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.
Pharmacology, Toxicology and Pharmaceutical Science
2
2%
Other
9
9%
Unknown
16
17%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 40. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 September 2026.
All research outputs
#1,314,818
of 34,528,520 outputs
Outputs from Cell Reports
#2,644
of 16,931 outputs
Outputs of similar age
#13,924
of 424,403 outputs
Outputs of similar age from Cell Reports
#31
of 177 outputs
Altmetric has tracked 34,528,520 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 96th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 16,931 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 26.9. This one has done well, scoring higher than 84% of its peers.
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We're also able to compare this research output to 177 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 82% of its contemporaries.
