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Metastatic group 3 ...
Metastatic group 3 medulloblastoma is driven by PRUNE1 targeting NME1–TGF-β–OTX2–SNAIL via PTEN inhibitio
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- Ferrucci, Veronica (author)
- Univ Napoli Federico II, Dipartimento Med Mol & Biotecnol Med, Naples, Italy;CEINGE Biotecnol Avanzate, Naples, Italy;European Sch Mol Med SEMM, Milan, Italy
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- de Antonellis, Pasqualino (author)
- Univ 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
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- Pennino, Francesco Paolo (author)
- Univ Napoli Federico II, Dipartimento Med Mol & Biotecnol Med, Naples, Italy;CEINGE Biotecnol Avanzate, Naples, Italy
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- Asadzadeh, Fatemeh (author)
- CEINGE Biotecnol Avanzate, Naples, Italy
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- Virgilio, Antonella (author)
- Univ Napoli Federico II, Dipartimento Farm, Naples, Italy
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- Montanaro, Donatella (author)
- CEINGE Biotecnol Avanzate, Naples, Italy
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- Galeone, Aldo (author)
- Univ Napoli Federico II, Dipartimento Farm, Naples, Italy
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- Boffa, Iolanda (author)
- CEINGE Biotecnol Avanzate, Naples, Italy
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- Pisano, Ida (author)
- CEINGE Biotecnol Avanzate, Naples, Italy
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- Scognamiglio, Iolanda (author)
- CEINGE Biotecnol Avanzate, Naples, Italy
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- Navas, Luigi (author)
- Univ Napoli Federico II, Dept Vet Med & Anim Prod, Naples, Italy
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- Diana, Donatella (author)
- CNR, Ist Biostrutture & Bioimmagini, Naples, Italy
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- Pedone, Emilia (author)
- CNR, Ist Biostrutture & Bioimmagini, Naples, Italy
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- Gargiulo, Sara (author)
- CNR, Ist Biostrutture & Bioimmagini, Naples, Italy
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- Gramanzini, Matteo (author)
- CNR, Ist Biostrutture & Bioimmagini, Naples, Italy
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- Brunetti, Arturo (author)
- CEINGE Biotecnol Avanzate, Naples, Italy;Univ Napoli Federico II, Dipartimento Sci Biomed Avanzate, Naples, Italy
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- Danielson, Laura (author)
- Inst Canc Res, Div Clin Studies, Sutton SM2 5NG, Surrey, England
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- Carotenuto, Marianeve (author)
- Univ Napoli Federico II, Dipartimento Med Mol & Biotecnol Med, Naples, Italy;CEINGE Biotecnol Avanzate, Naples, Italy
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- Liguori, Lucia (author)
- CEINGE Biotecnol Avanzate, Naples, Italy
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- Verrico, Antonio (author)
- Osped Santobono Pausilipon, Paediat Neurosurg, Naples, Italy
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- Quaglietta, Lucia (author)
- Osped Santobono Pausilipon, Paediat Neurosurg, Naples, Italy
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- Errico, Maria Elena (author)
- Osped Santobono Pausilipon, Pathol Unit, Naples, Italy
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- Del Monaco, Valentina (author)
- CEINGE Biotecnol Avanzate, Naples, Italy
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- D'Argenio, Valeria (author)
- Univ Napoli Federico II, Dipartimento Med Mol & Biotecnol Med, Naples, Italy;CEINGE Biotecnol Avanzate, Naples, Italy
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- Tirone, Felice (author)
- Fdn Santa Lucia, Natl Res Council, Inst Cell Biol & Neurobiol, Genet Control Dev URT, Rome, Italy
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- Mastronuzzi, Angela (author)
- IRCCS Osped Pediat Bambino Gesu, Dipartimento Oncoematol, Rome, Italy
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- Donofrio, Vittoria (author)
- Osped Santobono Pausilipon, Pathol Unit, Naples, Italy
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- Giangaspero, Felice (author)
- Univ Roma La Sapienza, Dipartimento Sci Radiol Oncol & Anatomo Patol, Rome, Italy;IRCCS Neuromed, Pozzilli, Italy
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- Picard, Daniel (author)
- Univ Hosp Dusseldorf, Dept Paediat Oncol Haematol & Clin Immunol, German Canc Consortium DKTK, Dusseldorf, Germany
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- Remke, Marc (author)
- Univ Hosp Dusseldorf, Dept Paediat Oncol Haematol & Clin Immunol, German Canc Consortium DKTK, Dusseldorf, Germany
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- Garzia, Livia (author)
- Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON, Canada;Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada
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- Daniels, Craig (author)
- Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON, Canada
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- Delattre, Olivier (author)
- PSL Res Univ, Inst Curie, Equipe Labellisue Ligue Canc, INSERM,U830, Paris, France
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- Johansson, Fredrik K., 1975- (author)
- Uppsala universitet,Neuroonkologi
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- Weiss, William A. (author)
- Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA
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- Salvatore, Francesco (author)
- Univ Napoli Federico II, Dipartimento Med Mol & Biotecnol Med, Naples, Italy;CEINGE Biotecnol Avanzate, Naples, Italy
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- Fattorusso, Roberto (author)
- Dipartimento Sci & Tecnol Ambientali, Biol & Farmaceut, Caserta, Italy
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- Chesler, Louis (author)
- Inst Canc Res, Div Clin Studies, Sutton SM2 5NG, Surrey, England
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- Taylor, Michael D. (author)
- Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON, Canada;Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada
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- Cinalli, Giuseppe (author)
- Osped Santobono Pausilipon, Paediat Neurosurg, Naples, Italy
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- Zollo, Massimo (author)
- Univ 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
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(creator_code:org_t)
- 2018-02-27
- 2018
- English.
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In: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 141:5, s. 1300-1319
- Related links:
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https://academic.oup...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- medulloblastoma
- metastatic CNS tumour
- molecular genetics
- genetic network
- oncology
Publication and Content Type
- ref (subject category)
- art (subject category)
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Brain
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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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Pisano, Ida
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Scognamiglio, Io ...
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Navas, Luigi
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Diana, Donatella
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Pedone, Emilia
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Gargiulo, Sara
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Gramanzini, Matt ...
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Brunetti, Arturo
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Danielson, Laura
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Carotenuto, Mari ...
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Liguori, Lucia
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Verrico, Antonio
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Quaglietta, Luci ...
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Errico, Maria El ...
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Del Monaco, Vale ...
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D'Argenio, Valer ...
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Tirone, Felice
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Mastronuzzi, Ang ...
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Donofrio, Vittor ...
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Giangaspero, Fel ...
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Picard, Daniel
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Remke, Marc
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Garzia, Livia
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Daniels, Craig
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Delattre, Olivie ...
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Johansson, Fredr ...
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Weiss, William A ...
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Salvatore, Franc ...
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Fattorusso, Robe ...
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Chesler, Louis
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Taylor, Michael ...
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Cinalli, Giusepp ...
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Zollo, Massimo
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Cancer and Oncol ...
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Brain
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Uppsala University