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The polarity protei...
The polarity protein Par3 coordinates positively self-renewal and negatively invasiveness in glioblastoma
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- Dadras, Mahsa Shahidi (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi,Weill Cornell Med, Brain & Mind Res Inst, New York, NY 10021 USA.
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- Caja, Laia (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab
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- Mezheyeuski, Artur (author)
- Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab
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- Liu, Sijia (author)
- Leiden Univ, Oncode Inst, Dept Cell & Chem Biol, Med Ctr, Leiden, Netherlands.
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- Gelabert, Caroline (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för medicinsk biokemi och mikrobiologi
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- Gomez-Puerto, Maria Catalina (author)
- Leiden Univ, Oncode Inst, Dept Cell & Chem Biol, Med Ctr, Leiden, Netherlands.
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- Gallini, Radiosa (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylära verktyg
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- Rubin, Carl-Johan (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab
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- ten Dijke, Peter (author)
- Leiden Univ, Oncode Inst, Dept Cell & Chem Biol, Med Ctr, Leiden, Netherlands.
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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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- Moustakas, Aristidis (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab
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(creator_code:org_t)
- 2021-10-12
- 2021
- English.
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In: Cell Death and Disease. - : Springer Nature. - 2041-4889. ; 12:10
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Abstract
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- Glioblastoma (GBM) is a brain malignancy characterized by invasiveness to the surrounding brain tissue and by stem-like cells, which propagate the tumor and may also regulate invasiveness. During brain development, polarity proteins, such as Par3, regulate asymmetric cell division of neuro-glial progenitors and neurite motility. We, therefore, studied the role of the Par3 protein (encoded by PARD3) in GBM. GBM patient transcriptomic data and patient-derived culture analysis indicated diverse levels of expression of PARD3 across and independent from subtypes. Multiplex immunolocalization in GBM tumors identified Par3 protein enrichment in SOX2-, CD133-, and NESTIN-positive (stem-like) cells. Analysis of GBM cultures of the three subtypes (proneural, classical, mesenchymal), revealed decreased gliomasphere forming capacity and enhanced invasiveness upon silencing Par3. GBM cultures with suppressed Par3 showed low expression of stemness (SOX2 and NESTIN) but higher expression of differentiation (GFAP) genes. Moreover, Par3 silencing reduced the expression of a set of genes encoding mitochondrial enzymes that generate ATP. Accordingly, silencing Par3 reduced ATP production and concomitantly increased reactive oxygen species. The latter was required for the enhanced migration observed upon silencing of Par3 as anti-oxidants blocked the enhanced migration. These findings support the notion that Par3 exerts homeostatic redox control, which could limit the tumor cell-derived pool of oxygen radicals, and thereby the tumorigenicity of GBM.
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)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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Dadras, Mahsa Sh ...
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Caja, Laia
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Mezheyeuski, Art ...
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Liu, Sijia
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Gelabert, Caroli ...
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Gomez-Puerto, Ma ...
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Gallini, Radiosa
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Rubin, Carl-Joha ...
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ten Dijke, Peter
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Heldin, Carl-Hen ...
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Moustakas, Arist ...
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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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MEDICAL AND HEAL ...
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Cell Death and D ...
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Uppsala University