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@ARTICLE{Foerster:303402,
author = {L. C. Foerster$^*$ and O. Kaya$^*$ and V. Wüst and D.-P.
Danciu and V. Akçay$^*$ and M. Bekavac$^*$ and K. C.
Ziegler$^*$ and N. Stinchcombe$^*$ and A. Tang$^*$ and S.
Kleber$^*$ and J. Tang$^*$ and J. Brunken$^*$ and I.
Lois-Bermejo$^*$ and N. Gesteira-Perez$^*$ and X. Ma$^*$ and
A. Sadik$^*$ and P. U. Le and K. Petrecca and C. Opitz$^*$
and H. Liu$^*$ and C. R. Wirtz and A. Goncalves$^*$ and A.
Marciniak-Czochra and S. Anders and A. Martin-Villalba$^*$},
title = {{C}ross-species comparison reveals therapeutic
vulnerabilities halting glioblastoma progression.},
journal = {Nature Communications},
volume = {16},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Springer Nature},
reportid = {DKFZ-2025-01638},
pages = {7250},
year = {2025},
note = {#EA:A290#LA:A290#},
abstract = {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.},
keywords = {Glioblastoma: genetics / Glioblastoma: pathology /
Glioblastoma: metabolism / Humans / Animals / Mice / DNA
Methylation / Disease Progression / Brain Neoplasms:
pathology / Brain Neoplasms: genetics / Brain Neoplasms:
metabolism / Gene Expression Regulation, Neoplastic /
Membrane Proteins: metabolism / Membrane Proteins: genetics
/ Neural Stem Cells: metabolism / Neural Stem Cells:
pathology / Intercellular Signaling Peptides and Proteins:
metabolism / Intercellular Signaling Peptides and Proteins:
genetics / Cell Line, Tumor / Neoplastic Stem Cells:
metabolism / Neoplastic Stem Cells: pathology / Female /
Male / Species Specificity / Prognosis / Membrane Proteins
(NLM Chemicals) / Intercellular Signaling Peptides and
Proteins (NLM Chemicals) / SFRP1 protein, human (NLM
Chemicals)},
cin = {A290 / A240 / B350 / HD01 / C220},
ddc = {500},
cid = {I:(DE-He78)A290-20160331 / I:(DE-He78)A240-20160331 /
I:(DE-He78)B350-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)C220-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40770193},
doi = {10.1038/s41467-025-62528-w},
url = {https://inrepo02.dkfz.de/record/303402},
}