Evidence map›Paper›PMID 20956948›Full record

ArticleOncogene2011

PKB/Akt promotes DSB repair in cancer cells through upregulating Mre11 expression following ionizing radiation.

R Deng, J Tang, J-G Ma, S-P Chen, L-P Xia, W-J Zhou, D-D Li, G-K Feng, Y-X Zeng, X-F Zhu

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 11% 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

48 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.

  1. Pooled it
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  16. CoA Synthase (Cancer research · 2020
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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

10 authors at 2 institutions in 1 country.

R DengState Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
J Tang
J-G Ma
S-P Chen
L-P Xia
W-J Zhou
D-D Li
G-K Feng
Y-X Zeng
X-F Zhu
Sun Yat-sen University · CNSun Yat-sen University Cancer Center · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

An elevated DNA-repair capacity in cancer cells leads to radiation resistance and severely limits the efficacy of radiation therapy. Activation of Akt is tightly associated with resistance to radiotherapy, and Mre11 protein has important role during the repair of DNA double-strand breaks (DSBs). In this report, our results showed that inhibition of Akt activity impaired the repair of DSBs in CNE2 cells, whereas activated Akt promoted the repair of DSBs in HeLa cells. Knockdown of Mre11 also impaired the process of DSB repair in both these two cell lines. More importantly, we found that Akt could regulate Mre11 expression. Inhibition of Akt activity by small interfering RNA or LY294002 efficiently downregulated the Mre11 expression in CNE2 cells, and transfection with myr-Akt plasmid in HeLa cells upregulated the Mre11 expression. In addition, luciferase reporter analysis revealed that Mre11 reporter activity increased after transfection with myr-Akt1 plasmids, and this myr-Akt1-induced transcriptional activity was blocked in the presence of LY294002. Further study showed GSK3β/β-catenin/LEF-1 pathway was involved in this regulation. Knockdown of β-catenin or LEF-1 led to the downregulation of Mre11, whereas overexpression of β-catenin led to upregulation of Mre11. The chromatin immunoprecipitation assay assay showed β-catenin/LEF-1 heterodimer could directly bind to the promoter of Mre11 in vivo. And the luciferase activity of the pGL3-Mre11 and pGL3-Lef increased in HeLa cells following β-catenin plasmid co-transfected, but was abolished when the LEF-1-binding conserved sequences of Mre11 promoter were mutated. These results together support Akt can upregulate the expression of Mre11 through GSK3β/ β-catenin/LEF pathway to elevate DSB-repair capacity in cancer cells.

Indexed as

beta CateninDNA-Binding ProteinsDNA Breaks, Double-StrandedDNA RepairEnzyme ActivationGene ExpressionGene Expression Regulation, NeoplasticGene Knockdown TechniquesGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaHeLa CellsHumansLymphoid Enhancer-Binding Factor 1MRE11 Homologue ProteinNeoplasmsOligonucleotide Array Sequence Analysisbeta CateninDNA-Binding ProteinsGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaGSK3B protein, humanLEF1 protein, humanLymphoid Enhancer-Binding Factor 1MRE11 Homologue ProteinMRE11 protein, humanProto-Oncogene Proteins c-akt

Identifiers

PMID20956948
OpenAlexW2059426385

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.