Home > Publications database > Cross-species comparison reveals therapeutic vulnerabilities halting glioblastoma progression. > print

001     303402
005     20250810022008.0
024 7 _ |a 10.1038/s41467-025-62528-w
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041 _ _ |a English
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100 1 _ |a Foerster, Leo Carl
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245 _ _ |a Cross-species comparison reveals therapeutic vulnerabilities halting glioblastoma progression.
260 _ _ |a [London]
|c 2025
|b Springer Nature
336 7 _ |a article
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520 _ _ |a The growth of a tumor is tightly linked to the distribution of its cells along a continuum of activation states. Here, we systematically decode the activation state architecture (ASA) in a glioblastoma (GBM) patient cohort through comparison to adult murine neural stem cells. Modelling of these data forecasts how tumor cells organize to sustain growth and identifies the rate of activation as the main predictor of growth. Accordingly, patients with a higher quiescence fraction exhibit improved outcomes. Further, DNA methylation arrays enable ASA-related patient stratification. Comparison of healthy and malignant gene expression dynamics reveals dysregulation of the Wnt-antagonist SFRP1 at the quiescence to activation transition. SFRP1 overexpression renders GBM quiescent and increases the overall survival of tumor-bearing mice. Surprisingly, it does so through reprogramming the tumor's stem-like methylome into an astrocyte-like one. Our findings offer a framework for patient stratification with prognostic value, biomarker identification, and therapeutic avenues to halt GBM progression.
536 _ _ |a 311 - Zellbiologie und Tumorbiologie (POF4-311)
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650 _ 7 |a Membrane Proteins
|2 NLM Chemicals
650 _ 7 |a Intercellular Signaling Peptides and Proteins
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650 _ 7 |a SFRP1 protein, human
|2 NLM Chemicals
650 _ 2 |a Glioblastoma: genetics
|2 MeSH
650 _ 2 |a Glioblastoma: pathology
|2 MeSH
650 _ 2 |a Glioblastoma: metabolism
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a DNA Methylation
|2 MeSH
650 _ 2 |a Disease Progression
|2 MeSH
650 _ 2 |a Brain Neoplasms: pathology
|2 MeSH
650 _ 2 |a Brain Neoplasms: genetics
|2 MeSH
650 _ 2 |a Brain Neoplasms: metabolism
|2 MeSH
650 _ 2 |a Gene Expression Regulation, Neoplastic
|2 MeSH
650 _ 2 |a Membrane Proteins: metabolism
|2 MeSH
650 _ 2 |a Membrane Proteins: genetics
|2 MeSH
650 _ 2 |a Neural Stem Cells: metabolism
|2 MeSH
650 _ 2 |a Neural Stem Cells: pathology
|2 MeSH
650 _ 2 |a Intercellular Signaling Peptides and Proteins: metabolism
|2 MeSH
650 _ 2 |a Intercellular Signaling Peptides and Proteins: genetics
|2 MeSH
650 _ 2 |a Cell Line, Tumor
|2 MeSH
650 _ 2 |a Neoplastic Stem Cells: metabolism
|2 MeSH
650 _ 2 |a Neoplastic Stem Cells: pathology
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Species Specificity
|2 MeSH
650 _ 2 |a Prognosis
|2 MeSH
700 1 _ |a Kaya, Oguzhan
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700 1 _ |a Wüst, Valentin
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700 1 _ |a Danciu, Diana-Patricia
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700 1 _ |a Akçay, Vuslat
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700 1 _ |a Bekavac, Milica
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700 1 _ |a Ziegler, Kevin Chris
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700 1 _ |a Stinchcombe, Nina
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700 1 _ |a Tang, Anna
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700 1 _ |a Gesteira-Perez, Noelia
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700 1 _ |a Ma, Xiujian
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700 1 _ |a Sadik, Ahmed
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700 1 _ |a Le, Phuong Uyen
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700 1 _ |a Petrecca, Kevin
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700 1 _ |a Opitz, Christiane
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700 1 _ |a Liu, Haikun
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700 1 _ |a Wirtz, Christian Rainer
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700 1 _ |a Goncalves, Angela
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700 1 _ |a Marciniak-Czochra, Anna
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700 1 _ |a Anders, Simon
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700 1 _ |a Martin-Villalba, Ana
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773 _ _ |a 10.1038/s41467-025-62528-w
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