TY - JOUR
T1 - Squelching glioblastoma stem cells by targeting REST for proteasomal degradation
AU - Zhang, Peisu
AU - Lathia, Justin D.
AU - Flavahan, William A.
AU - Rich, Jeremy N.
AU - Mattson, Mark P.
PY - 2009/11
Y1 - 2009/11
N2 - Glioblastoma brain tumors harbor a small population of cancer stem cells that are resistant to conventional chemotherapeutic and radiation treatments, and are believed responsible for tumor recurrence and mortality. The identification of the epigenetic molecular mechanisms that control self-renewal of glioblastoma stem cells will foster development of targeted therapeutic approaches. The transcriptional repressor REST, best known for its role in controlling cell fate decisions in neural progenitor cells, may also be crucial for cancer stem cell self-renewal. Two novel mechanisms for regulating the stability of REST have recently been revealed: these involve the telomere-binding protein TRF2 and the ubiquitin E3 ligase SCFβ-TrCP. Reduced TRF2 binding to REST, and increased SCFβ-TrCP activity, target REST for proteasomal degradation and thereby inhibit cancer stem cell proliferation. Neurological side effects of treatments that target REST and TRF2 may be less severe than conventional brain tumor treatments because postmitotic neurons do not express REST and have relatively stable telomeres.
AB - Glioblastoma brain tumors harbor a small population of cancer stem cells that are resistant to conventional chemotherapeutic and radiation treatments, and are believed responsible for tumor recurrence and mortality. The identification of the epigenetic molecular mechanisms that control self-renewal of glioblastoma stem cells will foster development of targeted therapeutic approaches. The transcriptional repressor REST, best known for its role in controlling cell fate decisions in neural progenitor cells, may also be crucial for cancer stem cell self-renewal. Two novel mechanisms for regulating the stability of REST have recently been revealed: these involve the telomere-binding protein TRF2 and the ubiquitin E3 ligase SCFβ-TrCP. Reduced TRF2 binding to REST, and increased SCFβ-TrCP activity, target REST for proteasomal degradation and thereby inhibit cancer stem cell proliferation. Neurological side effects of treatments that target REST and TRF2 may be less severe than conventional brain tumor treatments because postmitotic neurons do not express REST and have relatively stable telomeres.
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U2 - 10.1016/j.tins.2009.07.005
DO - 10.1016/j.tins.2009.07.005
M3 - Article
C2 - 19748686
AN - SCOPUS:70350018321
SN - 0166-2236
VL - 32
SP - 559
EP - 565
JO - Trends in Neurosciences
JF - Trends in Neurosciences
IS - 11
ER -