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22.09.2021 | Original Article

PAK3 is a key signature gene of the glioma proneural subtype and affects its proliferation, differentiation and growth

verfasst von: Nathalie Magne, Véronique Rousseau, Kévin Duarte, Sandrine Poëa-Guyon, Vincent Gleize, Alexandre Mutel, Charlotte Schmitt, Hélène Castel, Ahmed Idbaih, Emmanuelle Huillard, Marc Sanson, Jean-Vianney Barnier

Erschienen in: Cellular Oncology | Ausgabe 6/2021

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Abstract

Purpose

Gliomas are the most lethal adult primary brain cancers. Recent advances in their molecular characterization have contributed to a better understanding of their pathophysiology, but there is still a need to identify key genes controling glioma cell proliferation and differentiation. The p21-activated kinases PAK1 and PAK2 play essential roles in cell division and brain development and are well-known oncogenes. In contrast, the role of PAK3 in cancer is poorly understood. It is known, however, that this gene is involved in brain ontogenesis and has been identified as a gene of the proneural subtype signature in glioblastomas.

Methods

To better understand the role of PAK kinases in the pathophysiology of gliomas, we conducted expression analyses by querying multiple gene expression databases and analyzing primary human glioma samples. We next studied PAK3 expression upon differentiation in patient-derived cell lines (PDCLs) and the effects of PAK3 inhibition by lentiviral-mediated shRNA on glioma cell proliferation, differentiation and tumor growth.

Results

We show that contrary to PAK1 and PAK2, high PAK3 expression positively correlates with a longer survival of glioma patients. We also found that PAK3 displays differential expression patterns between glioma sub-groups with a higher expression in 1p/19q-codeleted oligodendrogliomas, and is highly expressed in tumors and PDCLs of the proneural subtype. In PDCLs, high PAK3 expression negatively correlated with proliferation and positively correlated with neuronal differentiation. Inhibition of PAK3 expression increased PDCL proliferation and glioma tumor growth in nude mice.

Conclusions

Our results indicate that PAK3 plays a unique role among PAKs in glioma development and may represent a potential therapeutic target.

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Titel: PAK3 is a key signature gene of the glioma proneural subtype and affects its proliferation, differentiation and growth
verfasst von: Nathalie Magne
Véronique Rousseau
Kévin Duarte
Sandrine Poëa-Guyon
Vincent Gleize
Alexandre Mutel
Charlotte Schmitt
Hélène Castel
Ahmed Idbaih
Emmanuelle Huillard
Marc Sanson
Jean-Vianney Barnier
Publikationsdatum: 22.09.2021
Verlag: Springer Netherlands
Erschienen in: Cellular Oncology / Ausgabe 6/2021
Print ISSN: 2211-3428
Elektronische ISSN: 2211-3436
DOI: https://doi.org/10.1007/s13402-021-00635-8

Springer Medizin

PAK3 is a key signature gene of the glioma proneural subtype and affects its proliferation, differentiation and growth

Abstract

Purpose

Methods

Results

Conclusions

Neu im Fachgebiet Pathologie

Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren

Personalisierte Medizin in der Onkologie

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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