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Metastatic group 3 ...
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Ferrucci, VeronicaUniv Napoli Federico II, Dipartimento Med Mol & Biotecnol Med, Naples, Italy;CEINGE Biotecnol Avanzate, Naples, Italy;European Sch Mol Med SEMM, Milan, Italy
(author)
Metastatic group 3 medulloblastoma is driven by PRUNE1 targeting NME1–TGF-β–OTX2–SNAIL via PTEN inhibitio
- Article/chapterEnglish2018
Publisher, publication year, extent ...
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2018-02-27
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Oxford University Press (OUP),2018
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-356501
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-356501URI
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https://doi.org/10.1093/brain/awy039DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Genetic modifications during development of paediatric groups 3 and 4 medulloblastoma are responsible for their highly metastatic properties and poor patient survival rates. PRUNE1 is highly expressed in metastatic medulloblastoma group 3, which is characterized by TGF-β signalling activation, c-MYC amplification, and OTX2 expression. We describe the process of activation of the PRUNE1 signalling pathway that includes its binding to NME1, TGF-β activation, OTX2 upregulation, SNAIL (SNAI1) upregulation, and PTEN inhibition. The newly identified small molecule pyrimido-pyrimidine derivative AA7.1 enhances PRUNE1 degradation, inhibits this activation network, and augments PTEN expression. Both AA7.1 and a competitive permeable peptide that impairs PRUNE1/NME1 complex formation, impair tumour growth and metastatic dissemination in orthotopic xenograft models with a metastatic medulloblastoma group 3 cell line (D425-Med cells). Using whole exome sequencing technology in metastatic medulloblastoma primary tumour cells, we also define 23 common ‘non-synonymous homozygous’ deleterious gene variants as part of the protein molecular network of relevance for metastatic processes. This PRUNE1/TGF-β/OTX2/PTEN axis, together with the medulloblastoma-driver mutations, is of relevance for future rational and targeted therapies for metastatic medulloblastoma group 3.
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de Antonellis, PasqualinoUniv Napoli Federico II, Dipartimento Med Mol & Biotecnol Med, Naples, Italy;CEINGE Biotecnol Avanzate, Naples, Italy;Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON, Canada
(author)
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Pennino, Francesco PaoloUniv Napoli Federico II, Dipartimento Med Mol & Biotecnol Med, Naples, Italy;CEINGE Biotecnol Avanzate, Naples, Italy
(author)
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Asadzadeh, FatemehCEINGE Biotecnol Avanzate, Naples, Italy
(author)
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Virgilio, AntonellaUniv Napoli Federico II, Dipartimento Farm, Naples, Italy
(author)
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Montanaro, DonatellaCEINGE Biotecnol Avanzate, Naples, Italy
(author)
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Galeone, AldoUniv Napoli Federico II, Dipartimento Farm, Naples, Italy
(author)
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Boffa, IolandaCEINGE Biotecnol Avanzate, Naples, Italy
(author)
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Pisano, IdaCEINGE Biotecnol Avanzate, Naples, Italy
(author)
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Scognamiglio, IolandaCEINGE Biotecnol Avanzate, Naples, Italy
(author)
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Navas, LuigiUniv Napoli Federico II, Dept Vet Med & Anim Prod, Naples, Italy
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Diana, DonatellaCNR, Ist Biostrutture & Bioimmagini, Naples, Italy
(author)
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Pedone, EmiliaCNR, Ist Biostrutture & Bioimmagini, Naples, Italy
(author)
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Gargiulo, SaraCNR, Ist Biostrutture & Bioimmagini, Naples, Italy
(author)
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Gramanzini, MatteoCNR, Ist Biostrutture & Bioimmagini, Naples, Italy
(author)
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Brunetti, ArturoCEINGE Biotecnol Avanzate, Naples, Italy;Univ Napoli Federico II, Dipartimento Sci Biomed Avanzate, Naples, Italy
(author)
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Danielson, LauraInst Canc Res, Div Clin Studies, Sutton SM2 5NG, Surrey, England
(author)
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Carotenuto, MarianeveUniv Napoli Federico II, Dipartimento Med Mol & Biotecnol Med, Naples, Italy;CEINGE Biotecnol Avanzate, Naples, Italy
(author)
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Liguori, LuciaCEINGE Biotecnol Avanzate, Naples, Italy
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Verrico, AntonioOsped Santobono Pausilipon, Paediat Neurosurg, Naples, Italy
(author)
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Quaglietta, LuciaOsped Santobono Pausilipon, Paediat Neurosurg, Naples, Italy
(author)
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Errico, Maria ElenaOsped Santobono Pausilipon, Pathol Unit, Naples, Italy
(author)
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Del Monaco, ValentinaCEINGE Biotecnol Avanzate, Naples, Italy
(author)
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D'Argenio, ValeriaUniv Napoli Federico II, Dipartimento Med Mol & Biotecnol Med, Naples, Italy;CEINGE Biotecnol Avanzate, Naples, Italy
(author)
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Tirone, FeliceFdn Santa Lucia, Natl Res Council, Inst Cell Biol & Neurobiol, Genet Control Dev URT, Rome, Italy
(author)
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Mastronuzzi, AngelaIRCCS Osped Pediat Bambino Gesu, Dipartimento Oncoematol, Rome, Italy
(author)
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Donofrio, VittoriaOsped Santobono Pausilipon, Pathol Unit, Naples, Italy
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Giangaspero, FeliceUniv Roma La Sapienza, Dipartimento Sci Radiol Oncol & Anatomo Patol, Rome, Italy;IRCCS Neuromed, Pozzilli, Italy
(author)
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Picard, DanielUniv Hosp Dusseldorf, Dept Paediat Oncol Haematol & Clin Immunol, German Canc Consortium DKTK, Dusseldorf, Germany
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Remke, MarcUniv Hosp Dusseldorf, Dept Paediat Oncol Haematol & Clin Immunol, German Canc Consortium DKTK, Dusseldorf, Germany
(author)
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Garzia, LiviaHosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON, Canada;Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada
(author)
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Daniels, CraigHosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON, Canada
(author)
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Delattre, OlivierPSL Res Univ, Inst Curie, Equipe Labellisue Ligue Canc, INSERM,U830, Paris, France
(author)
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Johansson, Fredrik K.,1975-Uppsala universitet,Neuroonkologi(Swepub:uu)fredjoha
(author)
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Weiss, William A.Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA
(author)
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Salvatore, FrancescoUniv Napoli Federico II, Dipartimento Med Mol & Biotecnol Med, Naples, Italy;CEINGE Biotecnol Avanzate, Naples, Italy
(author)
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Fattorusso, RobertoDipartimento Sci & Tecnol Ambientali, Biol & Farmaceut, Caserta, Italy
(author)
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Chesler, LouisInst Canc Res, Div Clin Studies, Sutton SM2 5NG, Surrey, England
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Taylor, Michael D.Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON, Canada;Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada
(author)
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Cinalli, GiuseppeOsped Santobono Pausilipon, Paediat Neurosurg, Naples, Italy
(author)
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Zollo, MassimoUniv Napoli Federico II, Dipartimento Med Mol & Biotecnol Med, Naples, Italy;CEINGE Biotecnol Avanzate, Naples, Italy;European Sch Mol Med SEMM, Milan, Italy;Azienda Osped Univ Federico II, DAI Med Trasfus, Naples, Italy
(author)
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Univ Napoli Federico II, Dipartimento Med Mol & Biotecnol Med, Naples, Italy;CEINGE Biotecnol Avanzate, Naples, Italy;European Sch Mol Med SEMM, Milan, ItalyUniv Napoli Federico II, Dipartimento Med Mol & Biotecnol Med, Naples, Italy;CEINGE Biotecnol Avanzate, Naples, Italy;Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON, Canada
(creator_code:org_t)
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In:Brain: Oxford University Press (OUP)141:5, s. 1300-13190006-89501460-2156
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Ferrucci, Veroni ...
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de Antonellis, P ...
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Pennino, Frances ...
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Asadzadeh, Fatem ...
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Virgilio, Antone ...
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Montanaro, Donat ...
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Galeone, Aldo
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Boffa, Iolanda
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Navas, Luigi
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Pedone, Emilia
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Verrico, Antonio
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