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

Abstract：

: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.

journal_name

Cell Stem Cell

journal_title

Cell stem cell

authors

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

doi

10.1016/j.stem.2016.12.001

subject

Has Abstract

pub_date

2017-04-06 00:00:00

pages

450-461.e4

issue

4

eissn

1934-5909

issn

1875-9777

pii

S1934-5909(16)30457-X

journal_volume

20

pub_type

杂志文章

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