Evidence map›Paper›PMID 21367844›Full record

ArticleEndocrine-related cancer2011

Histone deacetylase inhibitors upregulate Rap1GAP and inhibit Rap activity in thyroid tumor cells.

Xiaoyun Dong, Christopher Korch, Judy L Meinkoth

Open access · bronzeAbstract read
In one paragraph

Article in Endocrine-related cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.2field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 20 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 1 country.

Xiaoyun DongDepartment of Pharmacology, School of Medicine, University of Pennsylvania, Philadelphia, 19104 Pennsylvania, USA.
Christopher Korch
Judy L Meinkoth
University of Colorado Denver · USUniversity of Pennsylvania · US

Funding

Rap1Gap and Tumor ProgressionR01CA127986 · NCI · UNIVERSITY OF PENNSYLVANIA · PI MEINKOTH, JUDY L · 2009 to 2013
$1.6M
NCI NIH HHS CA127986NCI NIH HHS R01 CA127986
6 · The paper itself

Abstract

Increases in Rap activity have been associated with tumor progression. Although activating mutations in Rap have not been described, downregulation of Rap1GAP is frequent in human tumors including thyroid carcinomas. In this study, we explored whether endogenous Rap1GAP expression could be restored to thyroid tumor cells. The effects of deacetylase inhibitors and a demethylating agent, individually and in combination, were examined in four differentiated and six anaplastic thyroid carcinoma (ATC) cell lines. Treatment with the structurally distinct histone deacetylase (HDAC) inhibitors, sodium butyrate and trichostatin A, increased Rap1GAP expression in all the differentiated thyroid carcinoma cell lines and in four of the six ATC cell lines. The demethylating agent, 5-aza-deoxycytidine, restored Rap1GAP expression in one anaplastic cell line and enhanced the effects of HDAC inhibitors in a second anaplastic cell line. Western blotting indicated that Rap2 was highly expressed in human thyroid cancer cells. Importantly, treatment with HDAC inhibitors impaired Rap2 activity in both differentiated and anaplastic tumor cell lines. The mechanism through which Rap activity is repressed appears to entail effects on the expression of multiple Rap regulators, including RapGEFs and RapGAPs. These results suggest that HDAC inhibitors may provide a tractable approach to impair Rap activity in human tumor cells.

Indexed as

Adenocarcinoma, FollicularAzacitidineButyratesCarcinomaCarcinoma, PapillaryCell Line, TumorDecitabineDNA MethylationDrug Screening Assays, AntitumorDrug SynergismGene Expression Regulation, NeoplasticGTPase-Activating ProteinsHistone Deacetylase InhibitorsHumansHydroxamic AcidsNeoplasm ProteinsAzacitidineButyratesDecitabineGTPase-Activating ProteinsHistone Deacetylase InhibitorsHydroxamic AcidsNeoplasm ProteinsRAP1GAP protein, humanrap1 GTP-Binding ProteinsRAP2A protein, humanrap GTP-Binding ProteinsRNA, Small Interferingtrichostatin A

Identifiers

PMID21367844
PMCPMC3531977
OpenAlexW2104364004

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.