The critical role that STAT3 plays in glioma-initiating cells: STAT3 addiction in glioma

Oncotarget
Debolina GangulyLawrence M Pfeffer

Abstract

Glioma-Initiating Cells (GICs) are thought to be responsible for tumor initiation, progression and recurrence in glioblastoma (GBM). In previous studies, we reported the constitutive phosphorylation of the STAT3 transcription factor in GICs derived from GBM patient-derived xenografts, and that STAT3 played a critical role in GBM tumorigenesis. In this study, we show that CRISPR/Cas9-mediated deletion of STAT3 in an established GBM cell line markedly inhibited tumorigenesis by intracranial injection but had little effect on cell proliferation in vitro. Tumorigenesis was rescued by the enforced expression of wild-type STAT3 in cells lacking STAT3. In contrast, GICs were highly addicted to STAT3 and upon STAT3 deletion GICs were non-viable. Moreover, we found that STAT3 was constitutively activated in GICs by phosphorylation on both tyrosine (Y705) and serine (S727) residues. Therefore, to study STAT3 function in GICs we established an inducible system to knockdown STAT3 expression (iSTAT3-KD). Using this approach, we demonstrated that Y705-STAT3 phosphorylation was critical and indispensable for GIC-induced tumor formation. Both phosphorylation sites in STAT3 promoted GIC proliferation in vitro. We further showed that S727-STAT3 ...Continue Reading

References

Jul 18, 1995·Proceedings of the National Academy of Sciences of the United States of America·T G BoultonG D Yancopoulos
Feb 24, 1995·The Journal of Biological Chemistry·G S CampbellC Carter-Su
Jun 13, 2000·Oncogene·T BowmanR Jove
Mar 11, 2005·The New England Journal of Medicine·Roger StuppUNKNOWN National Cancer Institute of Canada Clinical Trials Group
Jul 23, 2005·Neoplasia : an International Journal for Oncology Research·Florian M CorvinusKarlheinz Friedrich
Mar 31, 2006·The Journal of Biological Chemistry·Hao H Ho, Lionel B Ivashkiv
Apr 6, 2006·Cancer Research·Edward A Sausville, Angelika M Burger
Jun 27, 2006·Nature·Andreas Androutsellis-TheotokisRonald D G McKay
Jan 16, 2007·Cancer Cell·Christopher CalabreseRichard J Gilbertson
May 2, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·Rong-Jane ChenYing-Jan Wang
Jan 10, 2009·Science·Joanna WegrzynAndrew C Larner
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Sep 4, 2010·International Journal of Interferon, Cytokine and Mediator Research : IJIM·Chuan He YangLawrence M Pfeffer
Apr 5, 2011·Pediatric Allergy and Immunology : Official Publication of the European Society of Pediatric Allergy and Immunology·Gui-Hong CaiDan Norbäck
May 7, 2011·Bioinformatics·Arthur LiberzonJill P Mesirov
Sep 24, 2011·The Journal of Biological Chemistry·Chuan He YangLawrence M Pfeffer
Jan 25, 2012·Gene Expression·Molly A TaylorWilliam P Schiemann
May 30, 2012·Nature Genetics·James R DowningWilliam E Evans
Jul 31, 2012·International Journal of Oncology·Hyang-Hwa RyuWoo-Yeol Jang
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Oct 15, 2013·Cell·Cameron W BrennanUNKNOWN TCGA Research Network
Sep 28, 2014·Bioinformatics·Simon AndersWolfgang Huber
Jan 24, 2015·Clinical and Experimental Medicine·Shi-Yao JiangShao-Li Deng
May 5, 2016·Nucleic Acids Research·Maxim V KuleshovAvi Ma'ayan
Jun 10, 2017·Journal of Neuro-oncology·Yu QinMadhuri Wadehra

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Citations

Mar 29, 2019·Pharmaceuticals·Debolina GangulyLawrence M Pfeffer
Nov 7, 2019·Cancers·Kelsey L PolakMark W Jackson
Oct 28, 2019·Cancers·Mohammad Khusni B Ahmat AminHisakazu Ogita
Jan 23, 2020·Biomolecules·Terezia KiskovaMonika Kassayova
Jan 10, 2019·Cancers·Sharon BerendsenPierre A Robe
Jan 16, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Anna M Krichevsky, Erik J Uhlmann
Oct 3, 2018·Journal of Cellular and Molecular Medicine·Hongjiang LiuBaohua Jiao
Nov 12, 2020·Nature Communications·Jason V GregoryJoerg Lahann
Feb 3, 2021·Journal of Cellular and Molecular Medicine·Yinan WangLawrence M Pfeffer
Dec 23, 2020·JCI Insight·Masahiro HitomiJustin D Lathia
Dec 1, 2020·Toxicology Reports·Athina-Maria AloizouEfthimios Dardiotis
May 28, 2021·Journal of Theoretical Biology·Tagari Samanta, Sandip Kar
Aug 10, 2021·Journal of Clinical Laboratory Analysis·Yang XuYuhai Zhang

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Methods Mentioned

BETA
surgical resection
xenograft
xenografts
RNA-seq
RNAseq
PCR

Software Mentioned

STATA
nCounter
nCounter Analysis System
MsigDB
nSolver
STAR
Living Image
STRONGARM
MP
bwa

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