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Inhibition of glioblastoma malignancy by Lgl1
lethal giant larvae (lgl) was first identified as a tumor suppressor in Drosophila, where its loss repressed the differentiation and promoted the invasion of neuroblasts, the Drosophila equivalent of the neural stem cell. Recently we have shown that a human homolog of Lgl, Lgl1 (LLGL1), is constitut...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4294391/ https://www.ncbi.nlm.nih.gov/pubmed/25426552 |
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author | Gont, Alexander Hanson, Jennifer E.L. Lavictoire, Sylvie J. Daneshmand, Manijeh Nicholas, Garth Woulfe, John Kassam, Amin Da Silva, Vasco F. Lorimer, Ian A.J. |
author_facet | Gont, Alexander Hanson, Jennifer E.L. Lavictoire, Sylvie J. Daneshmand, Manijeh Nicholas, Garth Woulfe, John Kassam, Amin Da Silva, Vasco F. Lorimer, Ian A.J. |
author_sort | Gont, Alexander |
collection | PubMed |
description | lethal giant larvae (lgl) was first identified as a tumor suppressor in Drosophila, where its loss repressed the differentiation and promoted the invasion of neuroblasts, the Drosophila equivalent of the neural stem cell. Recently we have shown that a human homolog of Lgl, Lgl1 (LLGL1), is constitutively phosphorylated and inactivated in glioblastoma cells; this occurs as a downstream consequence of PTEN loss, one of the most frequent genetic events in glioblastoma. Here we have investigated the consequences of this loss of functional Lgl1 in glioblastoma in vivo. We used a doxycycline-inducible system to express a non-phosphorylatable, constitutively active version of Lgl1 (Lgl3SA) in either a glioblastoma cell line or primary glioblastoma cells isolated under neural stem cell culture conditions from patients. In both types of cells, expression of Lgl3SA, but not wild type Lgl1, inhibited cell motility in vitro. Induction of Lgl3SA in intracerebral xenografts markedly reduced the in vivo invasion of primary glioblastoma cells. Lgl3SA expression also induced the differentiation of glioblastoma cells in vitro and in vivo along the neuronal lineage. Thus the central features of Lgl function as a tumor suppressor in Drosophila are conserved in human glioblastoma. |
format | Online Article Text |
id | pubmed-4294391 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-42943912015-01-21 Inhibition of glioblastoma malignancy by Lgl1 Gont, Alexander Hanson, Jennifer E.L. Lavictoire, Sylvie J. Daneshmand, Manijeh Nicholas, Garth Woulfe, John Kassam, Amin Da Silva, Vasco F. Lorimer, Ian A.J. Oncotarget Research Paper lethal giant larvae (lgl) was first identified as a tumor suppressor in Drosophila, where its loss repressed the differentiation and promoted the invasion of neuroblasts, the Drosophila equivalent of the neural stem cell. Recently we have shown that a human homolog of Lgl, Lgl1 (LLGL1), is constitutively phosphorylated and inactivated in glioblastoma cells; this occurs as a downstream consequence of PTEN loss, one of the most frequent genetic events in glioblastoma. Here we have investigated the consequences of this loss of functional Lgl1 in glioblastoma in vivo. We used a doxycycline-inducible system to express a non-phosphorylatable, constitutively active version of Lgl1 (Lgl3SA) in either a glioblastoma cell line or primary glioblastoma cells isolated under neural stem cell culture conditions from patients. In both types of cells, expression of Lgl3SA, but not wild type Lgl1, inhibited cell motility in vitro. Induction of Lgl3SA in intracerebral xenografts markedly reduced the in vivo invasion of primary glioblastoma cells. Lgl3SA expression also induced the differentiation of glioblastoma cells in vitro and in vivo along the neuronal lineage. Thus the central features of Lgl function as a tumor suppressor in Drosophila are conserved in human glioblastoma. Impact Journals LLC 2014-10-15 /pmc/articles/PMC4294391/ /pubmed/25426552 Text en Copyright: © 2014 Gont et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited |
spellingShingle | Research Paper Gont, Alexander Hanson, Jennifer E.L. Lavictoire, Sylvie J. Daneshmand, Manijeh Nicholas, Garth Woulfe, John Kassam, Amin Da Silva, Vasco F. Lorimer, Ian A.J. Inhibition of glioblastoma malignancy by Lgl1 |
title | Inhibition of glioblastoma malignancy by Lgl1 |
title_full | Inhibition of glioblastoma malignancy by Lgl1 |
title_fullStr | Inhibition of glioblastoma malignancy by Lgl1 |
title_full_unstemmed | Inhibition of glioblastoma malignancy by Lgl1 |
title_short | Inhibition of glioblastoma malignancy by Lgl1 |
title_sort | inhibition of glioblastoma malignancy by lgl1 |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4294391/ https://www.ncbi.nlm.nih.gov/pubmed/25426552 |
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