Evidence map›Paper›PMID 28812437›Full record

ArticleAutophagy2017

Autophagy-induced KDR/VEGFR-2 activation promotes the formation of vasculogenic mimicry by glioma stem cells.

Hai-Bo Wu, Shuai Yang, Hai-Yan Weng, Qian Chen, Xi-Long Zhao, Wen-Juan Fu, Qin Niu, Yi-Fang Ping, Ji Ming Wang, Xia Zhang and 2 more

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

Article in Autophagy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed, 1 pooled it
9.5field-weighted citation impact, top 1% 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

87 citing papers in PubMed, 1 synthesis or guideline pooled it, 157 citations in OpenAlex.

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27 more citing papers are in PubMed but not listed here.

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.

Hai-Bo Wua Institute of Pathology and Southwest Cancer Center, Southwest Hospital , Third Military Medical University, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China , Chongqing , China.
Shuai Yanga Institute of Pathology and Southwest Cancer Center, Southwest Hospital , Third Military Medical University, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China , Chongqing , China.
Hai-Yan Wengb Department of Pathology, the Affiliated Provincial Hospital , Anhui Medical University , Hefei , China.
Qian Chena Institute of Pathology and Southwest Cancer Center, Southwest Hospital , Third Military Medical University, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China , Chongqing , China.
Xi-Long Zhaoa Institute of Pathology and Southwest Cancer Center, Southwest Hospital , Third Military Medical University, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China , Chongqing , China.
Wen-Juan Fua Institute of Pathology and Southwest Cancer Center, Southwest Hospital , Third Military Medical University, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China , Chongqing , China.
Qin Niua Institute of Pathology and Southwest Cancer Center, Southwest Hospital , Third Military Medical University, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China , Chongqing , China.
Yi-Fang Pinga Institute of Pathology and Southwest Cancer Center, Southwest Hospital , Third Military Medical University, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China , Chongqing , China.
Ji Ming Wanga Institute of Pathology and Southwest Cancer Center, Southwest Hospital , Third Military Medical University, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China , Chongqing , China.
Xia Zhanga Institute of Pathology and Southwest Cancer Center, Southwest Hospital , Third Military Medical University, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China , Chongqing , China.
Xiao-Hong Yaoa Institute of Pathology and Southwest Cancer Center, Southwest Hospital , Third Military Medical University, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China , Chongqing , China.
Xiu-Wu Biana Institute of Pathology and Southwest Cancer Center, Southwest Hospital , Third Military Medical University, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China , Chongqing , China.
Army Medical University · CNAnhui Medical University · CNSouthwest Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antiangiogenesis with bevacizumab, an antibody against vascular endothelial growth factor (VEGF), has been used for devascularization to limit the growth of malignant glioma. However, the benefits are transient due to elusive mechanisms underlying resistance to the antiangiogenic therapy. Glioma stem cells (GSCs) are capable of forming vasculogenic mimicry (VM), an alternative microvascular circulation independent of VEGF-driven angiogenesis. Herein, we report that the formation of VM was promoted by bevacizumab-induced macroautophagy/autophagy in GSCs, which was associated with tumor resistance to antiangiogenic therapy. We established a 3-dimensional collagen scaffold to examine the formation of VM and autophagy by GSCs, and found that rapamycin increased the number of VM and enhanced KDR/VEGFR-2 phosphorylation. Treatment with chloroquine, or knockdown of the autophagy gene ATG5, inhibited the formation of VM and KDR phosphorylation in GSCs. Notably, neutralization of GSCs-produced VEGF with bevacizumab failed to recapitulate the effect of chloroquine treatment and ATG5 knockdown, suggesting that autophagy-promoted formation of VM was independent of tumor cell-derived VEGF. ROS was elevated when autophagy was induced in GSCs and activated KDR phosphorylation through the phosphoinositide 3-kinase (PI3K)-AKT pathway. A ROS inhibitor, N-acetylcysteine, abolished KDR phosphorylation and the formation of VM by GSCs. By examination of the specimens from 95 patients with glioblastoma, we found that ATG5 and p-KDR expression was strongly associated with the density of VM in tumors and poor clinical outcome. Our results thus demonstrate a crucial role of autophagy in the formation of VM by GSCs, which may serve as a therapeutic target in drug-resistant glioma.

Indexed as

AutophagyAnimalsAutophagy-Related Protein 5BevacizumabBrain NeoplasmsCell Line, TumorCell ProliferationChloroquineFemaleGene Knockdown TechniquesGliomaHumansMiceMice, SCIDModels, BiologicalNeoplastic Stem CellsAutophagy-Related Protein 5BevacizumabChloroquineReactive Oxygen SpeciesSirolimusVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2ATG5autophagyglioma stem cellsvasculogenic mimicryVEGFR-2

Identifiers

PMID28812437
PMCPMC5612353
OpenAlexW2750456514

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.