TY  - JOUR
AU  - Vanner, Robert J
AU  - Remke, Marc
AU  - Gallo, Marco
AU  - Selvadurai, Hayden J
AU  - Coutinho, Fiona
AU  - Lee, Lilian
AU  - Kushida, Michelle
AU  - Head, Renee
AU  - Morrissy, Sorana
AU  - Zhu, Xueming
AU  - Aviv, Tzvi
AU  - Voisin, Veronique
AU  - Clarke, Ian D
AU  - Li, Yisu
AU  - Mungall, Andrew J
AU  - Moore, Richard A
AU  - Ma, Yussanne
AU  - Jones, Steven J M
AU  - Marra, Marco A
AU  - Malkin, David
AU  - Northcott, Paul A
AU  - Kool, Marcel
AU  - Pfister, Stefan
AU  - Bader, Gary
AU  - Hochedlinger, Konrad
AU  - Korshunov, Andrey
AU  - Taylor, Michael D
AU  - Dirks, Peter B
TI  - Quiescent sox2(+) cells drive hierarchical growth and relapse in sonic hedgehog subgroup medulloblastoma.
JO  - Cancer cell
VL  - 26
IS  - 1
SN  - 1535-6108
CY  - Cambridge, Mass.
PB  - Cell Press
M1  - DKFZ-2018-00223
SP  - 33 - 47
PY  - 2014
AB  - Functional heterogeneity within tumors presents a significant therapeutic challenge. Here we show that quiescent, therapy-resistant Sox2(+) cells propagate sonic hedgehog subgroup medulloblastoma by a mechanism that mirrors a neurogenic program. Rare Sox2(+) cells produce rapidly cycling doublecortin(+) progenitors that, together with their postmitotic progeny expressing NeuN, comprise tumor bulk. Sox2(+) cells are enriched following anti-mitotic chemotherapy and Smoothened inhibition, creating a reservoir for tumor regrowth. Lineage traces from Sox2(+) cells increase following treatment, suggesting that this population is responsible for relapse. Targeting Sox2(+) cells with the antineoplastic mithramycin abrogated tumor growth. Addressing functional heterogeneity and eliminating Sox2(+) cells presents a promising therapeutic paradigm for treatment of sonic hedgehog subgroup medulloblastoma.
KW  - Antigens, Nuclear (NLM Chemicals)
KW  - Antineoplastic Agents (NLM Chemicals)
KW  - Biomarkers, Tumor (NLM Chemicals)
KW  - Hedgehog Proteins (NLM Chemicals)
KW  - Microtubule-Associated Proteins (NLM Chemicals)
KW  - Nerve Tissue Proteins (NLM Chemicals)
KW  - NeuN protein, mouse (NLM Chemicals)
KW  - Neuropeptides (NLM Chemicals)
KW  - Nuclear Proteins (NLM Chemicals)
KW  - Patched Receptors (NLM Chemicals)
KW  - Receptors, Cell Surface (NLM Chemicals)
KW  - Receptors, G-Protein-Coupled (NLM Chemicals)
KW  - SHH protein, human (NLM Chemicals)
KW  - SMO protein, human (NLM Chemicals)
KW  - SOX2 protein, human (NLM Chemicals)
KW  - SOXB1 Transcription Factors (NLM Chemicals)
KW  - Shh protein, mouse (NLM Chemicals)
KW  - Smo protein, mouse (NLM Chemicals)
KW  - Smoothened Receptor (NLM Chemicals)
KW  - Sox2 protein, mouse (NLM Chemicals)
KW  - doublecortin protein (NLM Chemicals)
KW  - neuronal nuclear antigen NeuN, human (NLM Chemicals)
KW  - Plicamycin (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:24954133
C2  - pmc:PMC4441014
DO  - DOI:10.1016/j.ccr.2014.05.005
UR  - https://inrepo02.dkfz.de/record/132541
ER  -