Evidence map›Paper›PMID 27740621›Full record

ArticleCell death and differentiation2017

Tetraspanin CD9 stabilizes gp130 by preventing its ubiquitin-dependent lysosomal degradation to promote STAT3 activation in glioma stem cells.

Yu Shi, Wenchao Zhou, Lin Cheng, Cong Chen, Zhi Huang, Xiaoguang Fang, Qiulian Wu, Zhicheng He, Senlin Xu, Justin D Lathia and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell death and differentiation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
5.1field-weighted citation impact, top 4% 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

51 citing papers in PubMed, 83 citations in OpenAlex.

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  9. Glioma-Derived Exosomes and Their Application as Drug Nanoparticles.International journal of molecular sciences · 2024
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 2 countries.

Yu ShiDepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Wenchao ZhouDepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Lin ChengState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University, Shanghai 200025, China.
Cong ChenDepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Zhi HuangDepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Xiaoguang FangDepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Qiulian WuDepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Zhicheng HeInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
Senlin XuInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
Justin D LathiaDepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Yifang PingInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
Jeremy N RichDepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Xiu-Wu BianInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
Shideng BaoDepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Cleveland Clinic Lerner College of Medicine · USSouthwest Hospital · CNArmy Medical University · CNShanghai Institute of Hematology · CN

Funding

Functional Inhibition of Deubiquitylase HAUSP to Disrupt Glioblastoma Stem CellsR01CA184090 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI BAO, SHIDENG · 2015 to 2019
$1.8M
Glioblastoma stem cell-derived pericytes and cancer invasionR01NS091080 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI BAO, SHIDENG · 2016 to 2020
$1.7M
Ubiquitination and Deubiquitination of c-Myc in GlioblastomaR01NS099175 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI BAO, SHIDENG · 2016 to 2020
$1.7M
LTQ-Orbitrap Velos instrumentS10RR031537 · NCRR · CLEVELAND CLINIC LERNER COM-CWRU · PI WILLARD, BELINDA BELLE · 2011 to 2011
$600k
NCI NIH HHS R01 CA184090NCRR NIH HHS S10 RR031537NINDS NIH HHS R01 NS091080NINDS NIH HHS R01 NS099175
6 · The paper itself

Abstract

Glioblastoma (GBM) is the most malignant and lethal brain tumor harboring glioma stem cells (GSCs) that promote tumor propagation and therapeutic resistance. GSCs preferentially express several critical cell surface molecules that regulate the pro-survival signaling for maintaining the stem cell-like phenotype. Tetraspanin CD9 has recently been reported as a GSC biomarker that is relevant to the GSC maintenance. However, the underlying molecular mechanisms of CD9 in maintaining GSC property remain elusive. Herein, we report that CD9 stabilizes the IL-6 receptor glycoprotein 130 (gp130) by preventing its ubiquitin-dependent lysosomal degradation to facilitate the STAT3 activation in GSCs. CD9 is preferentially expressed in GSCs of human GBM tumors. Mass spectrometry analysis identified gp130 as an interacting protein of CD9 in GSCs, which was confirmed by immunoprecipitation and immunofluorescent analyses. Disrupting CD9 or gp130 by shRNA significantly inhibited the self-renewal and promoted the differentiation of GSCs. Moreover, CD9 disruption markedly reduced gp130 protein levels and STAT3 activating phosphorylation in GSCs. CD9 stabilized gp130 by preventing its ubiquitin-dependent lysosomal degradation to promote the BMX-STAT3 signaling in GSCs. Importantly, targeting CD9 potently inhibited GSC tumor growth in vivo, while ectopic expression of the constitutively activated STAT3 (STAT3-C) restored the tumor growth impaired by CD9 disruption. Collectively, we uncovered a critical regulatory mechanism mediated by tetraspanin CD9 to maintain the stem cell-like property and tumorigenic potential of GSCs.

Indexed as

Amino Acid SequenceAnimalsBrain NeoplasmsCell Line, TumorCell ProliferationCell Self RenewalCytokine Receptor gp130FemaleGlioblastomaHumansImmunoprecipitationKaplan-Meier EstimateLysosomesMass SpectrometryMiceMice, Inbred C57BLCD9 protein, humanCytokine Receptor gp130PeptidesRNA, Small InterferingSTAT3 Transcription FactorTetraspanin 29Ubiquitin

Identifiers

PMID27740621
PMCPMC5260495
OpenAlexW2530604244

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.