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"posted-content", "published": "2023-03-31", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1158/0008-5472.c.6514337", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T12:10:28.433Z", "modified": "2026-08-20T12:10:29.634Z"}, {"entity": "publication", "iuid": "065e2ce2ee5b4c6bb5662444e9866769", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/065e2ce2ee5b4c6bb5662444e9866769.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/065e2ce2ee5b4c6bb5662444e9866769"}}, "title": "Dormant SOX9-Positive Cells Facilitate MYC-Driven Recurrence of Medulloblastoma.", "authors": [{"family": "Borgenvik", "given": "Anna", "initials": "A", "orcid": "0000-0003-4696-7703", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ca3b4c4e7b2b4fe4867c4e356957d4c9.json"}}, {"family": "Holmberg", "given": "Karl O", "initials": "KO", "orcid": "0000-0002-4402-0586", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/469c34ade5f34855880bd40a0ed93a5b.json"}}, {"family": "Bolin", "given": "Sara", "initials": "S", "orcid": "0000-0003-2835-1518", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/144233601c624bcd815822ff601d5e3e.json"}}, {"family": "Zhao", "given": "Miao", "initials": "M", "orcid": "0000-0002-4895-1177", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/75b5d6dc5cde46b8aca859fb961bf1de.json"}}, {"family": "Savov", "given": "Vasil", "initials": "V", "orcid": "0000-0003-2347-1975", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2e70244e16a3478e83abd7072ec7610b.json"}}, {"family": "Ros\u00e9n", "given": "Gabriela", "initials": "G", "orcid": "0000-0002-7762-1468", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c4bd52a448ba4dae883c2e14cddd2699.json"}}, {"family": "Hutter", "given": "Sonja", "initials": "S", "orcid": "0000-0003-3340-9315", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/68742a90cc194135a0eb33d52fe8b17a.json"}}, {"family": "Garancher", "given": "Alexandra", "initials": "A", "orcid": "0000-0001-5779-2860", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a08bf535ab73447baf9f6fef6a2a34cd.json"}}, {"family": "Rahmanto", "given": "Aldwin Suryo", "initials": "AS", "orcid": "0000-0002-4593-286X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/59328511ffe441f08443f83089cc909b.json"}}, {"family": "Bergstr\u00f6m", "given": "Tobias", "initials": "T", "orcid": "0000-0002-4557-2390", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ad8f5ab0560d4b7596ddd5e407b96d8f.json"}}, {"family": "Olsen", "given": "Thale Kristin", "initials": "TK", "orcid": "0000-0003-4655-7384", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/edb08108179a4b94a69eeca5809df636.json"}}, {"family": "Mainwaring", "given": "Oliver J", "initials": "OJ", "orcid": "0000-0002-7973-9849", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/29515b9bedc74325aa50a0da62cd299a.json"}}, {"family": "Sattanino", "given": "Damiana", "initials": "D", "orcid": "0000-0002-2747-4842", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e621b0c6b77443f083541dd2fd65ab34.json"}}, {"family": "Verbaan", "given": "Annemieke D", "initials": "AD", "orcid": "0000-0001-6793-0577", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/625389e761a746d6b9c65ab0c81d8582.json"}}, {"family": "Rusert", "given": "Jessica M", "initials": "JM", "orcid": "0000-0003-0751-2693", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/19ba859c845b4578b0b7fe729033c01a.json"}}, {"family": "Sundstr\u00f6m", "given": "Anders", "initials": "A", "orcid": "0000-0003-3942-6271", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/63e6602d2807417684239b93eb065a26.json"}}, {"family": "Bravo", "given": "Mar Ballester", "initials": "MB", "orcid": "0000-0002-1371-6679", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4fc8169b243f403bbb9d85a2cc51a20a.json"}}, {"family": "Dang", "given": "Yonglong", "initials": "Y", "orcid": "0000-0001-9705-5507", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a828f29d1e8f40a69087ea74c89bc32c.json"}}, {"family": "Wenz", "given": "Amelie S", "initials": "AS", "orcid": "0000-0003-1929-382X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/262d770d769340bc8cf743701280a879.json"}}, {"family": "Richardson", "given": "Stacey", "initials": "S", "orcid": "0000-0003-1841-6330", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bae77ca73b1845cb94fbae185a0d5d72.json"}}, {"family": "Fotaki", "given": "Grammatiki", "initials": "G", "orcid": "0000-0002-1343-1921", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b70b2fd7c1e348668fb7355bec1fcc3b.json"}}, {"family": "Hill", "given": "Rebecca M", "initials": "RM", "orcid": "0000-0001-8405-2219", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f1259bdc29b04296a844a8e51c538990.json"}}, {"family": "Dubuc", "given": "Adrian M", "initials": "AM", "orcid": "0000-0002-3447-6715", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/98d65b7575504dd7bc1419885b7c5bdd.json"}}, {"family": "Kalushkova", "given": "Antonia", "initials": "A", "orcid": "0000-0003-4535-506X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d630aa01038d4be68a001ae0fd4f3def.json"}}, {"family": "Remke", "given": "Marc", "initials": "M", "orcid": "0000-0002-9404-9993", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/975d2595635e45c49b84050b802a9251.json"}}, {"family": "\u010can\u010der", "given": "Matko", "initials": "M", "orcid": "0000-0001-5825-5151", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/05cbffef1ba74a4890860f33af1f5719.json"}}, {"family": "Jernberg-Wiklund", "given": "Helena", "initials": "H", "orcid": "0000-0002-9319-7986", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c1e229ba71ec4129ac7ca516f90838ef.json"}}, {"family": "Giraud", "given": "G\u00e9raldine", "initials": "G", "orcid": "0000-0002-2771-9889", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b71981055bfa4c1180c753e61b5b0919.json"}}, {"family": "Chen", "given": "Xingqi", "initials": "X", "orcid": "0000-0002-5657-2839", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ffb9d3c94e54fac97be6c78586940eb.json"}}, {"family": "Taylor", "given": "Michael D", "initials": "MD", "orcid": "0000-0001-7009-3466", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/619748747921467fa6c6ec4a973f2d1d.json"}}, {"family": "Sangfelt", "given": "Olle", "initials": "O", "orcid": "0000-0002-0316-0195", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2bc4930422a046f69295e2c59a569657.json"}}, {"family": "Clifford", "given": "Steven C", "initials": "SC", "orcid": "0000-0003-4893-2184", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fd7e72eebce545f99f8d96a4ead4b395.json"}}, {"family": "Sch\u00fcller", "given": "Ulrich", "initials": "U", "orcid": "0000-0002-8731-1121", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6bfed174354240068d313e96bc371611.json"}}, {"family": "Wechsler-Reya", "given": "Robert J", "initials": "RJ", "orcid": "0000-0002-7463-8352", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/36ca40f1c54d43d0af707c509bff1e9a.json"}}, {"family": "Weishaupt", "given": "Holger", "initials": "H", "orcid": "0000-0002-0364-2709", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6ae643d4831f469c95c3d5b3955784ea.json"}}, {"family": "Swartling", "given": "Fredrik J", "initials": "FJ", "orcid": "0000-0002-8460-4367", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2e673fa8c86348fb8c1a2ae34ba7ba9a.json"}}], "type": "journal article", "published": "2022-12-16", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "volume": "82", "issue": "24", "pages": "4586-4603", "issn-l": "0008-5472"}, "abstract": "Relapse is the leading cause of death in patients with medulloblastoma, the most common malignant pediatric brain tumor. A better understanding of the mechanisms underlying recurrence could lead to more effective therapies for targeting tumor relapses. Here, we observed that SOX9, a transcription factor and stem cell/glial fate marker, is limited to rare, quiescent cells in high-risk medulloblastoma with MYC amplification. In paired primary-recurrent patient samples, SOX9-positive cells accumulated in medulloblastoma relapses. SOX9 expression anti-correlated with MYC expression in murine and human medulloblastoma cells. However, SOX9-positive cells were plastic and could give rise to a MYC high state. To follow relapse at the single-cell level, an inducible dual Tet model of medulloblastoma was developed, in which MYC expression was redirected in vivo from treatment-sensitive bulk cells to dormant SOX9-positive cells using doxycycline treatment. SOX9 was essential for relapse initiation and depended on suppression of MYC activity to promote therapy resistance, epithelial-mesenchymal transition, and immune escape. p53 and DNA repair pathways were downregulated in recurrent tumors, whereas MGMT was upregulated. Recurrent tumor cells were found to be sensitive to treatment with an MGMT inhibitor and doxorubicin. These findings suggest that recurrence-specific targeting coupled with DNA repair inhibition comprises a potential therapeutic strategy in patients affected by medulloblastoma relapse.\n\nSOX9 facilitates therapy escape and recurrence in medulloblastoma via temporal inhibition of MYC/MYCN genes, revealing a strategy to specifically target SOX9-positive cells to prevent tumor relapse.", "doi": "10.1158/0008-5472.CAN-22-2108", "pmid": "36219398", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9755969"}, {"db": "pii", "key": "709709"}], "notes": [], "created": "2026-08-20T12:11:07.388Z", "modified": "2026-08-20T12:11:07.663Z"}, {"entity": "publication", "iuid": "dffb9a243b2544118016c0930cbc08bd", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/dffb9a243b2544118016c0930cbc08bd.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/dffb9a243b2544118016c0930cbc08bd"}}, "title": "The Irradiated Brain Microenvironment Supports Glioma Stemness and Survival via Astrocyte-Derived Transglutaminase 2.", "authors": [{"family": "Berg", "given": "Tracy J", "initials": "TJ"}, {"family": "Marques", "given": "Carolina", "initials": "C", "orcid": "0000-0002-8308-5630", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dc65829f36d243dc94f21a4650ed9c27.json"}}, {"family": "Pantazopoulou", "given": "Vasiliki", "initials": "V", "orcid": "0000-0002-5965-5795", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b4e8f1e6335241148a153f34611d9145.json"}}, {"family": "Johansson", "given": "Elinn", "initials": "E"}, {"family": "von Stedingk", "given": "Kristoffer", "initials": "K"}, {"family": "Lindgren", "given": "David", "initials": "D"}, {"family": "Jeannot", "given": "Pauline", "initials": "P", "orcid": "0000-0003-0158-440X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/167869db86f0456fbb7a535ae8d89b35.json"}}, {"family": "Pietras", "given": "Elin J", "initials": "EJ", "orcid": "0000-0002-5783-9347", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f9d48aa66cee48b9828c0ac374c75362.json"}}, {"family": "Bergstr\u00f6m", "given": "Tobias", "initials": "T", "orcid": "0000-0002-4557-2390", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ad8f5ab0560d4b7596ddd5e407b96d8f.json"}}, {"family": "Swartling", "given": "Fredrik J", "initials": "FJ", "orcid": "0000-0002-8460-4367", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2e673fa8c86348fb8c1a2ae34ba7ba9a.json"}}, {"family": "Governa", "given": "Valeria", "initials": "V"}, {"family": "Bengzon", "given": "Johan", "initials": "J"}, {"family": "Belting", "given": "Mattias", "initials": "M"}, {"family": "Axelson", "given": "H\u00e5kan", "initials": "H"}, {"family": "Squatrito", "given": "Massimo", "initials": "M"}, {"family": "Pietras", "given": "Alexander", "initials": "A", "orcid": "0000-0002-5783-9347", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f9d48aa66cee48b9828c0ac374c75362.json"}}], "type": "journal article", "published": "2021-04-15", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "volume": "81", "issue": "8", "pages": "2101-2115", "issn-l": "0008-5472"}, "abstract": "The tumor microenvironment plays an essential role in supporting glioma stemness and radioresistance. Following radiotherapy, recurrent gliomas form in an irradiated microenvironment. Here we report that astrocytes, when pre-irradiated, increase stemness and survival of cocultured glioma cells. Tumor-na\u00efve brains increased reactive astrocytes in response to radiation, and mice subjected to radiation prior to implantation of glioma cells developed more aggressive tumors. Extracellular matrix derived from irradiated astrocytes were found to be a major driver of this phenotype and astrocyte-derived transglutaminase 2 (TGM2) was identified as a promoter of glioma stemness and radioresistance. TGM2 levels increased after radiation in vivo and in recurrent human glioma, and TGM2 inhibitors abrogated glioma stemness and survival. These data suggest that irradiation of the brain results in the formation of a tumor-supportive microenvironment. Therapeutic targeting of radiation-induced, astrocyte-derived extracellular matrix proteins may enhance the efficacy of standard-of-care radiotherapy by reducing stemness in glioma. SIGNIFICANCE: These findings presented here indicate that radiotherapy can result in a tumor-supportive microenvironment, the targeting of which may be necessary to overcome tumor cell therapeutic resistance and recurrence. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/8/2101/F1.large.jpg.", "doi": "10.1158/0008-5472.CAN-20-1785", "pmid": "33483373", "labels": [], "xrefs": [{"db": "pii", "key": "0008-5472.CAN-20-1785"}], "notes": [], "created": "2026-08-20T12:11:03.084Z", "modified": "2026-08-20T12:11:03.255Z"}]}