TY  - JOUR
AU  - Metselaar, Dennis S
AU  - Meel, Michaël H
AU  - Goulding, Joshua R
AU  - du Chatinier, Aimeé
AU  - Rigamonti, Leyla
AU  - Waranecki, Piotr
AU  - Geisemeyer, Neal
AU  - de Gooijer, Mark C
AU  - Breur, Marjolein
AU  - Koster, Jan
AU  - Veldhuijzen van Zanten, Sophie E M
AU  - Bugiani, Marianna
AU  - Franke, Niels E
AU  - Reddy, Alyssa
AU  - Wesseling, Pieter
AU  - Kaspers, Gertjan J L
AU  - Hulleman, Esther
TI  - Gemcitabine therapeutically disrupts essential SIRT1-mediated p53 repression in atypical teratoid/rhabdoid tumors.
JO  - Cell reports / Medicine
VL  - 5
IS  - 9
SN  - 2666-3791
CY  - Maryland Heights, MO
PB  - Elsevier
M1  - DKFZ-2024-01780
SP  - 101700
PY  - 2024
N1  - 2024 Sep 17;5(9):101700
AB  - Atypical teratoid/rhabdoid tumors (ATRTs) are highly malignant embryonal tumors of the central nervous system with a dismal prognosis. Using a newly developed and validated patient-derived ATRT culture and xenograft model, alongside a panel of primary ATRT models, we found that ATRTs are selectively sensitive to the nucleoside analog gemcitabine. Gene expression and protein analyses indicate that gemcitabine treatment causes the degradation of sirtuin 1 (SIRT1), resulting in cell death through activation of nuclear factor κB (NF-κB) and p53. Furthermore, we discovered that gemcitabine-induced loss of SIRT1 results in a nucleus-to-cytoplasm translocation of the sonic hedgehog (SHH) signaling activator GLI2, explaining the observed additional gemcitabine sensitivity in SHH-subtype ATRT. Treatment of ATRT xenograft-bearing mice with gemcitabine resulted in a >30
KW  - ATRT (Other)
KW  - atypical teratoid/rhabdoid tumor (Other)
KW  - gemcitabine (Other)
KW  - neuro oncology (Other)
KW  - p53 (Other)
KW  - patient-derived models (Other)
KW  - pediatric oncology (Other)
KW  - sirtuin 1 (Other)
KW  - therapy development (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:39208799
DO  - DOI:10.1016/j.xcrm.2024.101700
UR  - https://inrepo02.dkfz.de/record/292537
ER  -