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Dadras MS, Caja L, Mezheyeuski A, et al. The polarity protein Par3 coordinates positively self-renewal and negatively invasiveness in glioblastoma. Cell Death Dis. 2021;12(10):932doi: 10.1038/s41419-021-04220-7.
Dadras, M. S., Caja, L., Mezheyeuski, A., Liu, S., Gélabert, C., Gomez-Puerto, M. C., Gallini, R., Rubin, C. J., Ten Dijke, P., Heldin, C. H., & Moustakas, A. (2021). The polarity protein Par3 coordinates positively self-renewal and negatively invasiveness in glioblastoma. Cell death & disease, 12(10), 932. https://doi.org/10.1038/s41419-021-04220-7
Dadras, Mahsa Shahidi, et al. "The polarity protein Par3 coordinates positively self-renewal and negatively invasiveness in glioblastoma." Cell death & disease vol. 12,10 (2021): 932. doi: https://doi.org/10.1038/s41419-021-04220-7
Dadras MS, Caja L, Mezheyeuski A, Liu S, Gélabert C, Gomez-Puerto MC, Gallini R, Rubin CJ, Ten Dijke P, Heldin CH, Moustakas A. The polarity protein Par3 coordinates positively self-renewal and negatively invasiveness in glioblastoma. Cell Death Dis. 2021 Oct 12;12(10):932. doi: 10.1038/s41419-021-04220-7. PMID: 34642295; PMCID: PMC8511086.
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Cell Death Dis. 2021 Oct 12;12(10):932. doi: 10.1038/s41419-021-04220-7.

The polarity protein Par3 coordinates positively self-renewal and negatively invasiveness in glioblastoma.

Cell death & disease

Mahsa Shahidi Dadras, Laia Caja, Artur Mezheyeuski, Sijia Liu, Caroline Gélabert, Maria Catalina Gomez-Puerto, Radiosa Gallini, Carl-Johan Rubin, Peter Ten Dijke, Carl-Henrik Heldin, Aristidis Moustakas

Affiliations

  1. Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Box 582, Biomedical Center, Uppsala University, SE-75123, Uppsala, Sweden.
  2. Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Science for Life Laboratory, Uppsala University, SE-75185, Uppsala, Sweden.
  3. Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, 10021, USA.
  4. Department of Cell and Chemical Biology, Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands.
  5. Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Box 582, Biomedical Center, Uppsala University, SE-75123, Uppsala, Sweden. [email protected].

PMID: 34642295 PMCID: PMC8511086 DOI: 10.1038/s41419-021-04220-7

Abstract

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.

© 2021. The Author(s).

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