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PRRX1 induced by BM...
PRRX1 induced by BMP signaling decreases tumorigenesis by epigenetically regulating glioma-initiating cell properties via DNA methyltransferase 3A
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- Tanabe, Ryo (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Univ Tokyo, Grad Sch Med, Dept Mol Pathol, Tokyo, Japan.
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- Miyazono, Kohei (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för medicinsk biokemi och mikrobiologi,Univ Tokyo, Grad Sch Med, Dept Mol Pathol, Tokyo, Japan.
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- Todo, Tomoki (author)
- Univ Tokyo, Inst Med Sci, Div Innovat Canc Therapy, Tokyo, Japan.
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- Saito, Nobuhito (author)
- Univ Tokyo, Grad Sch Med, Dept Neurosurg, Tokyo, Japan.
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- Iwata, Caname (author)
- Univ Tokyo, Grad Sch Med, Dept Mol Pathol, Tokyo, Japan.
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- Komuro, Akiyoshi (author)
- Univ Tokyo, Grad Sch Med, Dept Mol Pathol, Tokyo, Japan.
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- Sakai, Satoshi (author)
- Univ Tokyo, Grad Sch Med, Dept Mol Pathol, Tokyo, Japan.
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- Raja, Erna (author)
- Univ Tokyo, Grad Sch Med, Dept Mol Pathol, Tokyo, Japan.
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- Koinuma, Daizo (author)
- Univ Tokyo, Grad Sch Med, Dept Mol Pathol, Tokyo, Japan.
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- Morikawa, Masato (author)
- Univ Tokyo, Grad Sch Med, Dept Mol Pathol, Tokyo, Japan.
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- Westermark, Bengt (author)
- Uppsala Univ, Sci Life Lab, Rudbeck Lab, Dept Immunol Genet & Pathol, Uppsala, Sweden. Kindai Univ, Fac Med, Dept Biochem, Osaka, Japan. Asahi Kasei Pharma Corp, Lab Safety Assessment & ADME, Pharmaceut Res Ctr, Shizuoka, Japan.
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- Heldin, Carl-Henrik, 1952- (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för medicinsk biokemi och mikrobiologi
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(creator_code:org_t)
- 2021-07-16
- 2022
- English.
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In: Molecular Oncology. - : John Wiley & Sons. - 1574-7891 .- 1878-0261. ; 16:1, s. 269-288
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Abstract
Subject headings
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- Glioma-initiating cells (GICs), a major source of glioblastoma recurrence, are characterized by the expression of neural stem cell markers and the ability to grow by forming nonadherent spheres under serum-free conditions. Bone morphogenetic proteins (BMPs), members of the transforming growth factor-beta family, induce differentiation of GICs and suppress their tumorigenicity. However, the mechanisms underlying the BMP-induced loss of GIC stemness have not been fully elucidated. Here, we show that paired related homeobox 1 (PRRX1) induced by BMPs decreases the CD133-positive GIC population and inhibits tumorigenic activity of GICs in vivo. Of the two splice isoforms of PRRX1, the longer isoform, pmx-1b, but not the shorter isoform, pmx-1a, induces GIC differentiation. Upon BMP stimulation, pmx-1b interacts with the DNA methyltransferase DNMT3A and induces promoter methylation of the PROM1 gene encoding CD133. Silencing DNMT3A maintains PROM1 expression and increases the CD133-positive GIC population. Thus, pmx-1b promotes loss of stem cell-like properties of GICs through region-specific epigenetic regulation of CD133 expression by recruiting DNMT3A, which is associated with decreased tumorigenicity of GICs.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- BMP
- cancer-initiating cell
- CD133
- DNA methyltransferase
- glioblastoma
- PRRX1
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Tanabe, Ryo
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Miyazono, Kohei
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Todo, Tomoki
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Saito, Nobuhito
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Iwata, Caname
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Komuro, Akiyoshi
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Sakai, Satoshi
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Raja, Erna
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Koinuma, Daizo
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Morikawa, Masato
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Westermark, Beng ...
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Heldin, Carl-Hen ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Molecular Oncolo ...
- By the university
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Uppsala University