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Integrative Modelin...
Integrative Modeling Reveals Annexin A2-mediated Epigenetic Control of Mesenchymal Glioblastoma
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- Kling, Teresia, 1985 (author)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center,University of Gothenburg,Gothenburg Univ, Sahlgrenska Acad, Sahlgrenska Canc Ctr, Inst Biomed,Dept Pathol, S-41124 Gothenburg, Sweden.
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- Ferrarese, R. (author)
- Albert-Ludwigs-Universität Freiburg,University of Freiburg,Univ Freiburg, Fac Med, Med Ctr, Dept Neurosurg, Freiburg, Germany.
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- Ailin, D. O. (author)
- Albert-Ludwigs-Universität Freiburg,University of Freiburg,Univ Freiburg, Fac Med, Med Ctr, Dept Neurosurg, Freiburg, Germany.;Univ Freiburg, Fac Biol, Schnzlestr 1, D-79104 Freiburg, Germany.
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- Johansson, Patrik (author)
- Uppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab
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- Heiland, D. H. (author)
- Albert-Ludwigs-Universität Freiburg,University of Freiburg,Univ Freiburg, Fac Med, Med Ctr, Dept Neurosurg, Freiburg, Germany.
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- Dai, F. P. (author)
- Albert-Ludwigs-Universität Freiburg,University of Freiburg,Univ Freiburg, Fac Med, Med Ctr, Dept Neurosurg, Freiburg, Germany.
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- Vasilikos, I. (author)
- Albert-Ludwigs-Universität Freiburg,University of Freiburg,Univ Freiburg, Fac Med, Med Ctr, Dept Neurosurg, Freiburg, Germany.
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- Weyerbrock, A. (author)
- Albert-Ludwigs-Universität Freiburg,University of Freiburg,Univ Freiburg, Fac Med, Med Ctr, Dept Neurosurg, Freiburg, Germany.
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- Jörnsten, Rebecka, 1971 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för matematiska vetenskaper, matematisk statistik,Department of Mathematical Sciences, Mathematical Statistics,Chalmers tekniska högskola,Chalmers University of Technology,University of Gothenburg,Univ Gothenburg, Math Sci, SE-41296 Gothenburg, Sweden.;Chalmers, SE-41296 Gothenburg, Sweden.
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- Carro, M. S. (author)
- Albert-Ludwigs-Universität Freiburg,University of Freiburg,Univ Freiburg, Fac Med, Med Ctr, Dept Neurosurg, Freiburg, Germany.
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- Nelander, Sven (author)
- Uppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab
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(creator_code:org_t)
- Elsevier BV, 2016
- 2016
- English.
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In: Ebiomedicine. - : Elsevier BV. - 2352-3964. ; 12, s. 72-85
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Abstract
Subject headings
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- Glioblastomas are characterized by transcriptionally distinct subtypes, but despite possible clinical relevance, their regulation remains poorly understood. The commonly used molecular classification systems for GBM all identify a subtype with high expression of mesenchymal marker transcripts, strongly associated with invasive growth. We used a comprehensive data-driven network modeling technique (augmented sparse inverse covariance selection, aSICS) to define separate genomic, epigenetic, and transcriptional regulators of glioblastoma subtypes. Our model identified Annexin A2 (ANXA2) as a novel methylation-controlled positive regulator of the mesenchymal subtype. Subsequent evaluation in two independent cohorts established ANXA2 expression as a prognostic factor that is dependent on ANXA2 promoter methylation. ANXA2 knockdown in primary glioblastoma stem cell-like cultures suppressed known mesenchymal master regulators, and abrogated cell proliferation and invasion. Our results place ANXA2 at the apex of a regulatory cascade that determines glioblastoma mesenchymal transformation and validate aSICS as a general methodology to uncover regulators of cancer subtypes. (C) 2016 Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Bioinformatik och systembiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Bioinformatics and Systems Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Allmänmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- General Practice (hsv//eng)
Keyword
- Glioblastoma
- New methods for integrative data analysis
- Mesenchymal transformation
- Partial correlation based networks
- Brain tumor stem cells
- Annexin A2
- Master regulators of cancer cell phenotypes
- Epigenetic regulation
- Data integration
- Spare inve
- alternatively spliced segment
- human glioma-cells
- malignant glioma
- brain-tumors
- cancer cells
- tenascin-c
- in-vitro
- a2
- expression
- subtypes
- General & Internal Medicine
- ung cy
- 1994
- journal of cell biology
- v126
- p539
- Brain tumor stem cells
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Kling, Teresia, ...
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Ferrarese, R.
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Ailin, D. O.
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Johansson, Patri ...
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Heiland, D. H.
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Dai, F. P.
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show more...
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Vasilikos, I.
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Weyerbrock, A.
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Jörnsten, Rebeck ...
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Carro, M. S.
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Nelander, Sven
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Bioinformatics a ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and General Practice
- Articles in the publication
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Ebiomedicine
- By the university
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University of Gothenburg
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Chalmers University of Technology
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Uppsala University