ArticleGenome biology2015
P16-specific DNA methylation by engineered zinc finger methyltransferase inactivates gene transcription and promotes cancer metastasis.
Article in Genome biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 78 citations in OpenAlex.
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- DNMT3A loss drives a HIF-1-dependent synthetic lethality to HDAC6 inhibition in non-small cell lung cancer.Acta pharmaceutica Sinica. B · 2024Article
- P16iScience · 2024Article
- CDKN2A somatic copy number amplification in normal tissues surrounding gastric carcinoma reduces cancer metastasis risk in droplet digital PCR analysis.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024Article
- Molecular characteristics of early-onset pancreatic ductal adenocarcinoma.Molecular oncology · 2024Article
- The transcription activity ofTranslational cancer research · 2023Article
- Functional characterization of age-dependent p16 epimutation reveals biological drivers and therapeutic targets for colorectal cancer.Journal of experimental & clinical cancer research : CR · 2023Article
- Decreased sensitivity of cyclin-dependent kinase 4/6 inhibitors, palbociclib and abemaciclib to canine lymphoma cells with high p16 protein expression and low retinoblastoma protein phosphorylation.The Journal of veterinary medical science · 2023Article
- Efficient generation of epigenetic disease model mice by epigenome editing using the piggyBac transposon system.Epigenetics & chromatin · 2022Article
- Enzyme-free targeted DNA demethylation using CRISPR-dCas9-based steric hindrance to identify DNA methylation marks causal to altered gene expression.Nature protocols · 2022Review
- Kaiso phosphorylation at threonine 606 leads to its accumulation in the cytoplasm, reducing its transcriptional repression of the tumour suppressor CDH1.Molecular oncology · 2022Article
- Detection of somatic copy number deletion of theFrontiers in oncology · 2022Article
- Gene-Targeted DNA Methylation: Towards Long-Lasting Reprogramming of Gene Expression?Advances in experimental medicine and biology · 2022Review
- Pancreatic Progenitor Commitment Is Marked by an Increase in Ink4a/Arf Expression.Biomolecules · 2021Article
- A novel DNA methylation-based model that effectively predicts prognosis in hepatocellular carcinoma.Bioscience reports · 2021Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundP16 DNA methylation is well known to be the most frequent event in cancer development. It has been reported that genetic inactivation of P16 drives cancer growth and metastasis, however, whether P16 DNA methylation is truly a driver in cancer metastasis remains unknown.
resultsA P16-specific DNA methyltransferase (P16-dnmt) expression vector is designed using a P16 promoter-specific engineered zinc finger protein fused with the catalytic domain of dnmt3a. P16-dnmt transfection significantly decreases P16 promoter activity, induces complete methylation of P16 CpG islands, and inactivates P16 transcription in the HEK293T cell line. The P16-Dnmt coding fragment is integrated into an expression controllable vector and used to induce P16-specific DNA methylation in GES-1 and BGC823 cell lines. Transwell assays show enhanced migration and invasion of these cancer cells following P16-specific DNA methylation. Such effects are not observed in the P16 mutant A549 cell line. These results are confirmed using an experimental mouse pneumonic metastasis model. Moreover, enforced overexpression of P16 in these cells reverses the migration phenotype. Increased levels of RB phosphorylation and NFκB subunit P65 expression are also seen following P16-specific methylation and might further contribute to cancer metastasis.
conclusionP16 methylation could directly inactivate gene transcription and drive cancer metastasis.
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