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Driving Neuronal Di...
Driving Neuronal Differentiation through Reversal of an ERK1/2-miR-124-SOX9 Axis Abrogates Glioblastoma Aggressiveness
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- Sabelström, H. (författare)
- University of California System
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- Petri, Rebecca (författare)
- Lund University,Lunds universitet,Molekylär neurogenetik,Forskargrupper vid Lunds universitet,Molecular Neurogenetics,Lund University Research Groups
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- Shchors, Ksenya (författare)
- Pfizer Inc. US
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- Jandial, R. (författare)
- City of Hope National Medical Center
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- Schmidt, Christin (författare)
- University of California System
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- Sacheva, Rohit (författare)
- Lund University
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- Masic, S. (författare)
- University of California System
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- Yuan, E. (författare)
- University of California System
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- Fenster, Trenten (författare)
- University of California System
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- Martinez, Michael (författare)
- University of Texas Health Science Centre,UCSF Helen Diller Family Comprehensive Cancer Center
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- Saxena, S. (författare)
- University of California System
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- Nicolaides, Theodore P. (författare)
- University of California System
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- Ilkhanizadeh, Shirin (författare)
- University of California System
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- Berger, Mitchel S. (författare)
- University of California System
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- Snyder, Evan Y. (författare)
- University of California, San Diego
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- Weiss, William A. (författare)
- University of California System
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- Jakobsson, J. (författare)
- Lund University,Lunds universitet,Molekylär neurogenetik,Forskargrupper vid Lunds universitet,Molecular Neurogenetics,Lund University Research Groups
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- Persson, Anders I. (författare)
- University of California System
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(creator_code:org_t)
- Elsevier BV, 2019
- 2019
- Engelska.
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 28:8, s. 11-2079
- Relaterad länk:
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http://dx.doi.org/10... (free)
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http://www.cell.com/...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Identifying cellular programs that drive cancers to be stem-like and treatment resistant is critical to improving outcomes in patients. Here, we demonstrate that constitutive extracellular signal-regulated kinase 1/2 (ERK1/2) activation sustains a stem-like state in glioblastoma (GBM), the most common primary malignant brain tumor. Pharmacological inhibition of ERK1/2 activation restores neurogenesis during murine astrocytoma formation, inducing neuronal differentiation in tumorspheres. Constitutive ERK1/2 activation globally regulates miRNA expression in murine and human GBMs, while neuronal differentiation of GBM tumorspheres following the inhibition of ERK1/2 activation requires the functional expression of miR-124 and the depletion of its target gene SOX9. Overexpression of miR124 depletes SOX9 in vivo and promotes a stem-like-to-neuronal transition, with reduced tumorigenicity and increased radiation sensitivity. Providing a rationale for reports demonstrating miR-124-induced abrogation of GBM aggressiveness, we conclude that reversal of an ERK1/2-miR-124-SOX9 axis induces a neuronal phenotype and that enforcing neuronal differentiation represents a therapeutic strategy to improve outcomes in GBM. Sabelström et al. show that the loss of neurogenesis is reversible during neural stem cell-derived glioma formation. Pharmacological inhibition of ERK1/2 globally regulates miRNAs and induces neuronal differentiation, a process that is dependent on the modulation of an miR-124-SOX9 axis in glioblastoma (GBM) cells. The overexpression of miR-124 induces neuronal differentiation that abrogates GBM aggressiveness.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- brain
- cancer
- differentiation
- glioblastoma
- glioma
- microRNA
- neural stem cell
- neurogenesis
- neuron
- tumor
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
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Sabelström, H.
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Petri, Rebecca
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Shchors, Ksenya
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Jandial, R.
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Schmidt, Christi ...
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Sacheva, Rohit
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visa fler...
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Masic, S.
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Yuan, E.
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Fenster, Trenten
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Martinez, Michae ...
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Saxena, S.
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Nicolaides, Theo ...
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Ilkhanizadeh, Sh ...
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Berger, Mitchel ...
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Snyder, Evan Y.
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Weiss, William A ...
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Jakobsson, J.
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Persson, Anders ...
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visa färre...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Cell och molekyl ...
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Cell Reports
- Av lärosätet
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Lunds universitet