Journal Article

DKFZ-2024-01877

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png SOX10 mediates glioblastoma cell-state plasticity.

Man, K. H. (First author)DKFZ* ; Wu, Y. ; Gao, Z. ; Spreng, A.-S.DKFZ* ; Keding, S. J. E.DKFZ* ; Mangei, J.DKFZ* ; Boskovic, P.DKFZ* ; Mallm, J.-P.DKFZ* ; Liu, H.-K.DKFZ* ; Imbusch, C. D.DKFZ* ; Lichter, P.DKFZ* ; Radlwimmer, B. (Last author)DKFZ*

2024
Wiley Hoboken, NJ [u.a.]

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Please use a persistent id in citations: doi:10.1038/s44319-024-00258-8

Abstract: Phenotypic plasticity is a cause of glioblastoma therapy failure. We previously showed that suppressing the oligodendrocyte-lineage regulator SOX10 promotes glioblastoma progression. Here, we analyze SOX10-mediated phenotypic plasticity and exploit it for glioblastoma therapy design. We show that low SOX10 expression is linked to neural stem-cell (NSC)-like glioblastoma cell states and is a consequence of temozolomide treatment in animal and cell line models. Single-cell transcriptome profiling of Sox10-KD tumors indicates that Sox10 suppression is sufficient to induce tumor progression to an aggressive NSC/developmental-like phenotype, including a quiescent NSC-like cell population. The quiescent NSC state is induced by temozolomide and Sox10-KD and reduced by Notch pathway inhibition in cell line models. Combination treatment using Notch and HDAC/PI3K inhibitors extends the survival of mice carrying Sox10-KD tumors, validating our experimental therapy approach. In summary, SOX10 suppression mediates glioblastoma progression through NSC/developmental cell-state transition, including the induction of a targetable quiescent NSC state. This work provides a rationale for the design of tumor therapies based on single-cell phenotypic plasticity analysis.

Keyword(s): SOX10 ; Glioblastoma ; Phenotypic Plasticity ; Therapy Resistance ; Tumor Cell Quiescence

Note: #EA:B060#LA:B060# / 2024 Nov;25(11):5113-5140

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Contributing Institute(s):

1. B060 Molekulare Genetik (B060)
2. Angewandte Bioinformatik (B330)
3. A240 Molekulare Neurogenetik (A240)
4. scOpen Lab (W192)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2024

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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