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2017 ; 20
(4
): 450-461.e4
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English Wikipedia
Glioblastoma Cancer Stem Cells Evade Innate Immune Suppression of Self-Renewal
through Reduced TLR4 Expression
#MMPMID28089910
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
Cell Stem Cell
2017[Apr]; 20
(4
): 450-461.e4
PMID28089910
show ga
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.