Title :

ALDH1L2 Knockout in U251 Glioblastoma Cells Reduces Tumor Sphere Formation by Increasing Oxidative Stress and Suppressing Methionine Dependency

Author(s) :

Quéré, Maëlle [Auteur]
Alberto, Jean-Marc [Auteur]
Broly, Franck [Auteur]
Pôle de Biologie Pathologie Génétique [CHU Lille]
Hergalant, Sébastien [Auteur]
Christov, Christo [Auteur]
Gauchotte, Guillaume [Auteur]
Guéant, Jean-Louis [Auteur]
Namour, Farès [Auteur]
Battaglia-Hsu, Shyue-Fang [Auteur]

Journal title :

Nutrients

Abbreviated title :

Nutrients

Volume number :

14

Pages :

1887

Publisher :

MDPI

Publication date :

2022-04-30

ISSN :

2072-6643

English keyword(s) :

tumor sphere
glioblastoma
methionine
ROS

HAL domain(s) :

Sciences du Vivant [q-bio]
Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Biochimie [q-bio.BM]
Informatique [cs]/Bio-informatique [q-bio.QM]
Sciences du Vivant [q-bio]/Alimentation et Nutrition
Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Biologie moléculaire
Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Génomique, Transcriptomique et Protéomique [q-bio.GN]
Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Réseaux moléculaires [q-bio.MN]
Sciences du Vivant [q-bio]/Cancer
Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Anatomie, Histologie, Anatomopathologie [q-bio.TO]

English abstract : [en]

Previously, the in vitro growth of cancer stem cells in the form of tumor spheres from five different brain cancer cell lines was found to be methionine-dependent. As this earlier work indicated that ALDH1L2, a folate-dependent ...
Show more >Previously, the in vitro growth of cancer stem cells in the form of tumor spheres from five different brain cancer cell lines was found to be methionine-dependent. As this earlier work indicated that ALDH1L2, a folate-dependent mitochondria aldehyde dehydrogenase gene, is upregulated in glioblastoma stem cells, we invalidated this gene using CRISPR-cas 9 technique in this present work. We reported here that this invalidation was effective in U251 glioblastoma cells, and no cas9 off target site could be detected by genome sequencing of the two independent knockout targeting either exon I or exon III. The knockout of ALDH1L2 gene in U251 cells rendered the growth of the cancer stem cells of U251 methionine independent. In addition, a much higher ROS (reactive oxygen radicals) level can be detected in the knockout cells compared to the wild type cells. Our evidence here linked the excessive ROS level of the knockout cells to reduced total cellular NADPH. Our evidence suggested also that the cause of the slower growth of the knockout turmor sphere may be related to its partial differentiation.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CHU Lille
Institut Pasteur de Lille

Collections :

• Autres travaux scientifiques

Submission date :

2023-10-20T06:06:31Z
2024-02-28T15:56:40Z