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SFRP2 induces a mes...
SFRP2 induces a mesenchymal subtype transition by suppression of SOX2 in glioblastoma
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- Guo, Min (författare)
- Karolinska Inst, Dept Oncol Pathol, BioClinicum, Solna, Sweden.;Capital Med Univ, Beijing Tiantan Hosp, Dept Radiol, Beijing, Peoples R China.
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- Goudarzi, Kaveh M. (författare)
- Karolinska Inst, Dept Oncol Pathol, Sci Life Lab, Solna, Sweden.
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- Abedi, Shiva (författare)
- Karolinska Inst, Dept Oncol Pathol, BioClinicum, Solna, Sweden.
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- Pieber, Melanie (författare)
- Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, Solna, Sweden.
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- Sjöberg, Elin (författare)
- Uppsala universitet,Vaskulärbiologi
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- Behnan, Jinan (författare)
- Karolinska Inst, Dept Med Biochem & Biophys, Div Mol Neurobiol, Solna, Sweden.;Albert Einstein Coll Med, Dept Neurosurg, Bronx, NY 10467 USA.
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- Zhang, Xing-Mei (författare)
- Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, Solna, Sweden.
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- Harris, Robert A. (författare)
- Karolinska Institutet,Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, Solna, Sweden.
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- Bartek, Jiri (författare)
- Karolinska Institutet,Karolinska Inst, Dept Med Biochem & Biophys, Solna, Sweden.;Danish Canc Soc Res Ctr, Copenhagen, Denmark.
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- Lindström, Mikael S. (författare)
- Karolinska Institutet,Karolinska Inst, Dept Med Biochem & Biophys, Solna, Sweden.
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- Nistér, Monica (författare)
- Karolinska Institutet,Karolinska Inst, Dept Oncol Pathol, BioClinicum, Solna, Sweden.
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- Hägerstrand, Daniel (författare)
- Karolinska Institutet,Karolinska Inst, Dept Oncol Pathol, BioClinicum, Solna, Sweden.;Karolinska Inst, Dept Mol Med & Surg, BioClinicum, Solna, Sweden.
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Karolinska Inst, Dept Oncol Pathol, BioClinicum, Solna, Sweden;Capital Med Univ, Beijing Tiantan Hosp, Dept Radiol, Beijing, Peoples R China. Karolinska Inst, Dept Oncol Pathol, Sci Life Lab, Solna, Sweden. (creator_code:org_t)
- 2021-05-21
- 2021
- Engelska.
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Ingår i: Oncogene. - : Springer Nature. - 0950-9232 .- 1476-5594. ; 40:32, s. 5066-5080
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Intratumoral heterogeneity is a characteristic of glioblastomas that contain an intermixture of cell populations displaying different glioblastoma subtype gene expression signatures. Proportions of these populations change during tumor evolution, but the occurrence and regulation of glioblastoma subtype transition is not well described. To identify regulators of glioblastoma subtypes we utilized a combination of in vitro experiments and in silico analyses, using experimentally generated as well as publicly available data. Through this combined approach SOX2 was identified to confer a proneural glioblastoma subtype gene expression signature. SFRP2 was subsequently identified as a SOX2-antagonist, able to induce a mesenchymal glioblastoma subtype signature. A subset of patient glioblastoma samples with high SFRP2 and low SOX2 expression was particularly enriched with mesenchymal subtype samples. Phenotypically, SFRP2 decreased tumor sphere formation, stemness as assessed by limiting dilution assay, and overall cell proliferation but increased cell motility, whereas SOX2 induced the opposite effects. Furthermore, an SFRP2/non-canonical-WNT/KLF4/PDGFR/phospho-AKT/SOX2 signaling axis was found to be involved in the mesenchymal transition. Analysis of human tumor tissue spatial gene expression patterns showed distinct expression of SFRP2- and SOX2-correlated genes in vascular and cellular areas, respectively. Finally, conditioned media from SFRP2 overexpressing cells increased CD206 on macrophages. Together, these findings present SFRP2 as a SOX2-antagonist with the capacity to induce a mesenchymal subtype transition in glioma cells located in vascular tumor areas, highlighting its role in glioblastoma tumor evolution and intratumoral heterogeneity.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
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Oncogene
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- Av författaren/redakt...
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Guo, Min
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Goudarzi, Kaveh ...
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Abedi, Shiva
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Pieber, Melanie
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Sjöberg, Elin
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Behnan, Jinan
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visa fler...
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Zhang, Xing-Mei
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Harris, Robert A ...
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Bartek, Jiri
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Lindström, Mikae ...
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Nistér, Monica
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Hägerstrand, Dan ...
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Uppsala universitet
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Karolinska Institutet