Integrative Modeling Reveals Annexin A2-mediated Epigenetic Control of Mesenchymal Glioblastoma
Kling T, Ferrarese R, Ó hAilín D, Johansson P, Heiland DH, Dai F, Vasilikos I, Weyerbrock A, Jörnsten R, Carro MS, Nelander S (2016)
Publication Type: Journal article
Publication year: 2016
Journal
Book Volume: 12
Pages Range: 72-85
DOI: 10.1016/j.ebiom.2016.08.050
Abstract
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.
Authors with CRIS profile
Involved external institutions
Universitätsklinikum Freiburg
Germany (DE)
Uppsala University
Sweden (SE)
University of Gothenburg / Göteborgs universitet
Sweden (SE)
Chalmers University of Technology / Chalmers tekniska högskola
Sweden (SE)
Germany (DE)
Uppsala University
Sweden (SE)
University of Gothenburg / Göteborgs universitet
Sweden (SE)
Chalmers University of Technology / Chalmers tekniska högskola
Sweden (SE)
How to cite
APA:
Kling, T., Ferrarese, R., Ó hAilín, D., Johansson, P., Heiland, D.H., Dai, F.,... Nelander, S. (2016). Integrative Modeling Reveals Annexin A2-mediated Epigenetic Control of Mesenchymal Glioblastoma. EBioMedicine, 12, 72-85. https://doi.org/10.1016/j.ebiom.2016.08.050
MLA:
Kling, Teresia, et al. "Integrative Modeling Reveals Annexin A2-mediated Epigenetic Control of Mesenchymal Glioblastoma." EBioMedicine 12 (2016): 72-85.
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