%0 Journal Article
%A Vanner, Robert J
%A Remke, Marc
%A Gallo, Marco
%A Selvadurai, Hayden J
%A Coutinho, Fiona
%A Lee, Lilian
%A Kushida, Michelle
%A Head, Renee
%A Morrissy, Sorana
%A Zhu, Xueming
%A Aviv, Tzvi
%A Voisin, Veronique
%A Clarke, Ian D
%A Li, Yisu
%A Mungall, Andrew J
%A Moore, Richard A
%A Ma, Yussanne
%A Jones, Steven J M
%A Marra, Marco A
%A Malkin, David
%A Northcott, Paul A
%A Kool, Marcel
%A Pfister, Stefan
%A Bader, Gary
%A Hochedlinger, Konrad
%A Korshunov, Andrey
%A Taylor, Michael D
%A Dirks, Peter B
%T Quiescent sox2(+) cells drive hierarchical growth and relapse in sonic hedgehog subgroup medulloblastoma.
%J Cancer cell
%V 26
%N 1
%@ 1535-6108
%C Cambridge, Mass.
%I Cell Press
%M DKFZ-2018-00223
%P 33 - 47
%D 2014
%X 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.
%K Antigens, Nuclear (NLM Chemicals)
%K Antineoplastic Agents (NLM Chemicals)
%K Biomarkers, Tumor (NLM Chemicals)
%K Hedgehog Proteins (NLM Chemicals)
%K Microtubule-Associated Proteins (NLM Chemicals)
%K Nerve Tissue Proteins (NLM Chemicals)
%K NeuN protein, mouse (NLM Chemicals)
%K Neuropeptides (NLM Chemicals)
%K Nuclear Proteins (NLM Chemicals)
%K Patched Receptors (NLM Chemicals)
%K Receptors, Cell Surface (NLM Chemicals)
%K Receptors, G-Protein-Coupled (NLM Chemicals)
%K SHH protein, human (NLM Chemicals)
%K SMO protein, human (NLM Chemicals)
%K SOX2 protein, human (NLM Chemicals)
%K SOXB1 Transcription Factors (NLM Chemicals)
%K Shh protein, mouse (NLM Chemicals)
%K Smo protein, mouse (NLM Chemicals)
%K Smoothened Receptor (NLM Chemicals)
%K Sox2 protein, mouse (NLM Chemicals)
%K doublecortin protein (NLM Chemicals)
%K neuronal nuclear antigen NeuN, human (NLM Chemicals)
%K Plicamycin (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:24954133
%2 pmc:PMC4441014
%R 10.1016/j.ccr.2014.05.005
%U https://inrepo02.dkfz.de/record/132541