Glioblastoma Cancer Stem Cells Evade Innate Immune Suppression of Self-Renewal through Reduced TLR4 Expression.


:Tumors contain hostile inflammatory signals generated by aberrant proliferation, necrosis, and hypoxia. These signals are sensed and acted upon acutely by the Toll-like receptors (TLRs) to halt proliferation and activate an immune response. Despite the presence of TLR ligands within the microenvironment, tumors progress, and the mechanisms that permit this growth remain largely unknown. We report that self-renewing cancer stem cells (CSCs) in glioblastoma have low TLR4 expression that allows them to survive by disregarding inflammatory signals. Non-CSCs express high levels of TLR4 and respond to ligands. TLR4 signaling suppresses CSC properties by reducing retinoblastoma binding protein 5 (RBBP5), which is elevated in CSCs. RBBP5 activates core stem cell transcription factors, is necessary and sufficient for self-renewal, and is suppressed by TLR4 overexpression in CSCs. Our findings provide a mechanism through which CSCs persist in hostile environments because of an inability to respond to inflammatory signals.


Cell Stem Cell


Cell stem cell


Alvarado AG,Thiagarajan PS,Mulkearns-Hubert EE,Silver DJ,Hale JS,Alban TJ,Turaga SM,Jarrar A,Reizes O,Longworth MS,Vogelbaum MA,Lathia JD




Has Abstract


2017-04-06 00:00:00














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    authors: Rando TA,Ambrosio F

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  • TGF-β Pathway Inhibition Signals New Hope for Fanconi Anemia.

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    pub_type: 杂志文章


    authors: Murata K,Jadhav U,Madha S,van Es J,Dean J,Cavazza A,Wucherpfennig K,Michor F,Clevers H,Shivdasani RA

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    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Barker N,Huch M,Kujala P,van de Wetering M,Snippert HJ,van Es JH,Sato T,Stange DE,Begthel H,van den Born M,Danenberg E,van den Brink S,Korving J,Abo A,Peters PJ,Wright N,Poulsom R,Clevers H

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    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Zhang RR,Cui QY,Murai K,Lim YC,Smith ZD,Jin S,Ye P,Rosa L,Lee YK,Wu HP,Liu W,Xu ZM,Yang L,Ding YQ,Tang F,Meissner A,Ding C,Shi Y,Xu GL

    更新日期:2013-08-01 00:00:00

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    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Zhu Y,Smith DJ,Zhou Y,Li YR,Yu J,Lee D,Wang YC,Di Biase S,Wang X,Hardoy C,Ku J,Tsao T,Lin LJ,Pham AT,Moon H,McLaughlin J,Cheng D,Hollis RP,Campo-Fernandez B,Urbinati F,Wei L,Pang L,Rezek V,Berent-Maoz B,Ma

    更新日期:2019-10-03 00:00:00

  • Patents and misplaced angst: lessons for translational stem cell research from genomics.

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    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Mathews DJ,Cook-Deegan R,Bubela T

    更新日期:2013-05-02 00:00:00

  • Kit regulates HSC engraftment across the human-mouse species barrier.

    abstract::In-depth analysis of the cellular and molecular mechanisms regulating human HSC function will require a surrogate host that supports robust maintenance of transplanted human HSCs in vivo, but the currently available options are problematic. Previously we showed that mutations in the Kit receptor enhance engraftment of...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Cosgun KN,Rahmig S,Mende N,Reinke S,Hauber I,Schäfer C,Petzold A,Weisbach H,Heidkamp G,Purbojo A,Cesnjevar R,Platz A,Bornhäuser M,Schmitz M,Dudziak D,Hauber J,Kirberg J,Waskow C

    更新日期:2014-08-07 00:00:00