Evidence map›Paper›PMID 21052095›Full record

ArticleCell death and differentiation2011

Molecular characterization of apoptosis induced by CARF silencing in human cancer cells.

C T Cheung, R Singh, A R Yoon, M K Hasan, T Yaguchi, S C Kaul, C O Yun, R Wadhwa

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in Cell death and differentiation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
0.4field-weighted citation impact, top 37% 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

15 citing papers in PubMed, 27 citations in OpenAlex.

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4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

8 authors at 3 institutions in 3 countries.

C T CheungNational Institute of Advanced Industrial Science & Technology (AIST), Central 4, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8562, Japan.
R Singh
A R Yoon
M K Hasan
T Yaguchi
S C Kaul
C O Yun
R Wadhwa
National Institute of Advanced Industrial Science and Technology · JPYonsei University · KRCity of Hope · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Collaborator of ARF (CARF) was cloned as an ARF-interacting protein and shown to regulate the p53-p21(WAF1)-HDM2 pathway, which is central to tumor suppression via senescence and apoptosis. We had previously reported that CARF inhibition in cancer cells led to polyploidy and caspase-dependent apoptosis, however, the mechanisms governing this phenomenon remained unknown. Thus, we examined various cell death and survival pathways including the mitochondrial stress, ataxia telangiectasia mutated (ATM)-ATR, Ras-MAP kinase and retinoblastoma cascades. We found that CARF is a pleiotropic regulator with widespread effects; its suppression affected all investigated pathways. Most remarkably, it protected the cells against genotoxicity; CARF knockdown elicited DNA damage response as evidenced by increased levels of phosphorylated ATM and γH2AX, leading to induction of mitotic arrest and eventual apoptosis. We also show that the CARF-silencing-induced apoptosis in vitro translates to in vivo. In a human tumor xenograft mouse model, treatment of developing tumors with short hairpin RNA (shRNA) against CARF via an adenovirus carrier induced complete suppression of tumor growth, suggesting that CARF shRNA is a strong candidate for an anticancer reagent. We demonstrate that CARF has a vital role in genome preservation and tumor suppression and CARF siRNA is an effective novel cancer therapeutic agent.

Indexed as

ApoptosisAnimalsAntineoplastic AgentsApoptosis Regulatory ProteinsAtaxia Telangiectasia Mutated ProteinsCell Cycle ProteinsCell Line, TumorDNA-Binding ProteinsDNA RepairHistonesHumansMiceMice, NudeNeoplasmsPhosphorylationProtein Serine-Threonine KinasesAntineoplastic AgentsApoptosis Regulatory ProteinsAtaxia Telangiectasia Mutated ProteinsATM protein, humanAtm protein, mouseCDKN2AIP protein, humanCell Cycle ProteinsDNA-Binding ProteinsHistonesProtein Serine-Threonine KinasesRNA-Binding ProteinsRNA, Small InterferingTumor Suppressor Proteins

Identifiers

PMID21052095
PMCPMC3131902
OpenAlexW2068036116

What OpenQuestion holds

Textmetadata
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.