Evidence map›Paper›PMID 30986607›Full record

ArticleRedox biology2019

Dual blockage of STAT3 and ERK1/2 eliminates radioresistant GBM cells.

Bowen Xie, Lu Zhang, Wenfeng Hu, Ming Fan, Nian Jiang, Yumei Duan, Di Jing, Wenwu Xiao, Ruben C Fragoso, Kit S Lam and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Redox biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.4field-weighted citation impact, top 10% 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

28 citing papers in PubMed, 37 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

12 authors at 3 institutions in 2 countries.

Bowen XieCenter for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, China; Key Laboratory of Molecular Radiation Oncology Hunan Province, Changsha, China; Department of Radiation Oncology, University of California Davis School of Medicine, Sacramento, CA, 95817, USA.
Lu ZhangCenter for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, China; Key Laboratory of Molecular Radiation Oncology Hunan Province, Changsha, China; Department of Radiation Oncology, University of California Davis School of Medicine, Sacramento, CA, 95817, USA.
Wenfeng HuCenter for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, China; Key Laboratory of Molecular Radiation Oncology Hunan Province, Changsha, China.
Ming FanDepartment of Radiation Oncology, University of California Davis School of Medicine, Sacramento, CA, 95817, USA.
Nian JiangDepartment of Radiation Oncology, University of California Davis School of Medicine, Sacramento, CA, 95817, USA.
Yumei DuanDepartment of Pathology, Xiangya Hospital, Central South University, Changsha, China.
Di JingDepartment of Radiation Oncology, University of California Davis School of Medicine, Sacramento, CA, 95817, USA.
Wenwu XiaoDepartment of Biochemistry and Molecular Medicine, University of California Davis School of Medicine, Sacramento, CA, USA; NCI-Designated Comprehensive Cancer Center, University of California Davis School of Medicine, Sacramento, CA, USA.
Ruben C FragosoDepartment of Radiation Oncology, University of California Davis School of Medicine, Sacramento, CA, 95817, USA; NCI-Designated Comprehensive Cancer Center, University of California Davis School of Medicine, Sacramento, CA, USA.
Kit S LamDepartment of Biochemistry and Molecular Medicine, University of California Davis School of Medicine, Sacramento, CA, USA; NCI-Designated Comprehensive Cancer Center, University of California Davis School of Medicine, Sacramento, CA, USA.
Lun-Quan SunCenter for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, China; Key Laboratory of Molecular Radiation Oncology Hunan Province, Changsha, China. Electronic address: lunquansun@csu.edu.cn.
Jian Jian LiDepartment of Radiation Oncology, University of California Davis School of Medicine, Sacramento, CA, 95817, USA; NCI-Designated Comprehensive Cancer Center, University of California Davis School of Medicine, Sacramento, CA, USA. Electronic address: jijli@ucdavis.edu.
University of California, Davis · USCentral South University · CNXiangya Hospital Central South University · CN

Funding

Staff InvestigatorsP30CA093373 · NCI · UNIVERSITY OF CALIFORNIA DAVIS · PI Gina M Dayton · 2002 to 2026
$84.9M
NCI NIH HHS P30 CA093373
6 · The paper itself

Abstract

Radiotherapy (RT) is the major modality for control of glioblastoma multiforme (GBM), the most aggressive brain tumor in adults with poor prognosis and low patient survival rate. To improve the RT efficacy on GBM, the mechanism causing tumor adaptive radioresistance which leads to the failure of tumor control and lethal progression needs to be further elucidated. Here, we conducted a comparative analysis of RT-treated recurrent tumors versus primary counterparts in GBM patients, RT-treated orthotopic GBM tumors xenografts versus untreated tumors and radioresistant GBM cells versus wild type cells. The results reveal that activation of STAT3, a well-defined redox-sensitive transcriptional factor, is causally linked with GBM adaptive radioresistance. Database analysis also agrees with the worse prognosis in GBM patients due to the STAT3 expression-associated low RT responsiveness. However, although the radioresistant GBM cells can be resensitized by inhibition of STAT3, a fraction of radioresistant cells can still survive the RT combined with STAT3 inhibition or CRISPR/Cas9-mediated STAT3 knockout. A complementally enhanced activation of ERK1/2 by STAT3 inhibition is identified responsible for the survival of the remaining resistant tumor cells. Dual inhibition of ERK1/2 and STAT3 remarkably eliminates resistant GBM cells and inhibits tumor regrowth. These findings demonstrate a previously unknown feature ofSTAT3-mediated ERK1/2 regulation and an effective combination of two targets in resensitizing GBM to RT.

Indexed as

Radiation ToleranceAnimalsCell Line, TumorDisease Models, AnimalEnzyme ActivationGene ExpressionGenes, ReporterGlioblastomaHumansMiceMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3MutationPrognosisSTAT3 Transcription FactorMAPK3 protein, humanMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3STAT3 protein, humanSTAT3 Transcription FactorERK1/2GBMRadioresistanceRadiotherapySTAT3Tumor regrowth

Identifiers

PMID30986607
PMCPMC6463934
OpenAlexW2937840200

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.