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| 001 | 293327 | ||
| 005 | 20250523121147.0 | ||
| 024 | 7 | _ | |a 10.1038/s44319-024-00258-8 |2 doi |
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| 037 | _ | _ | |a DKFZ-2024-01877 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 570 |
| 100 | 1 | _ | |a Man, Ka Hou |0 P:(DE-He78)54ffbd220f4f40801144e564197dd3d4 |b 0 |e First author |u dkfz |
| 245 | _ | _ | |a SOX10 mediates glioblastoma cell-state plasticity. |
| 260 | _ | _ | |a Hoboken, NJ [u.a.] |c 2024 |b Wiley |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1732103303_4248 |2 PUB:(DE-HGF) |
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| 500 | _ | _ | |a #EA:B060#LA:B060# / 2024 Nov;25(11):5113-5140 |
| 520 | _ | _ | |a 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. |
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| 650 | _ | 7 | |a SOX10 |2 Other |
| 650 | _ | 7 | |a Glioblastoma |2 Other |
| 650 | _ | 7 | |a Phenotypic Plasticity |2 Other |
| 650 | _ | 7 | |a Therapy Resistance |2 Other |
| 650 | _ | 7 | |a Tumor Cell Quiescence |2 Other |
| 700 | 1 | _ | |a Wu, Yonghe |b 1 |
| 700 | 1 | _ | |a Gao, Zhenjiang |b 2 |
| 700 | 1 | _ | |a Spreng, Anna-Sophie |0 P:(DE-He78)c4c258d44a86b1ab0d1c5d7370a4a916 |b 3 |u dkfz |
| 700 | 1 | _ | |a Keding, Sigrun Johanna Elisabeth |0 P:(DE-He78)4009b389a34f8d3f41368959e7fd8e6a |b 4 |
| 700 | 1 | _ | |a Mangei, Jasmin |0 P:(DE-He78)1bf78749dde0284a02c44a5153fba925 |b 5 |
| 700 | 1 | _ | |a Boskovic, Pavle |0 P:(DE-He78)843808e53ce583be326cf75564db3bdd |b 6 |
| 700 | 1 | _ | |a Mallm, Jan-Philipp |0 P:(DE-He78)697cb039ca08f3b7e5a2a52dbf020b46 |b 7 |u dkfz |
| 700 | 1 | _ | |a Liu, Hai-Kun |0 P:(DE-He78)76aeb2431f7458c9261e69c5420390c6 |b 8 |u dkfz |
| 700 | 1 | _ | |a Imbusch, Charles D |0 0000-0003-4920-551X |b 9 |
| 700 | 1 | _ | |a Lichter, Peter |0 P:(DE-He78)e13b4363c5fe858044ef8a39c02c870c |b 10 |u dkfz |
| 700 | 1 | _ | |a Radlwimmer, Bernhard |0 P:(DE-He78)d1939d434dd885fad08106329e3db719 |b 11 |e Last author |u dkfz |
| 773 | _ | _ | |a 10.1038/s44319-024-00258-8 |0 PERI:(DE-600)2025376-X |n 11 |p 5113-5140 |t EMBO reports |v 25 |y 2024 |x 1469-221X |
| 856 | 4 | _ | |u https://inrepo02.dkfz.de/record/293327/files/man-et-al-sox10-mediates-glioblastoma-cell-state-plasticity-1.pdf |
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