Cargando…
Genome-Wide RNAi Screening Identifies Genes Inhibiting the Migration of Glioblastoma Cells
Glioblastoma Multiforme (GBM) cells are highly invasive, infiltrating into the surrounding normal brain tissue, making it impossible to completely eradicate GBM tumors by surgery or radiation. Increasing evidence also shows that these migratory cells are highly resistant to cytotoxic reagents, but d...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3625150/ https://www.ncbi.nlm.nih.gov/pubmed/23593504 http://dx.doi.org/10.1371/journal.pone.0061915 |
_version_ | 1782266072080056320 |
---|---|
author | Yang, Jian Fan, Jing Li, Ying Li, Fuhai Chen, Peikai Fan, Yubo Xia, Xiaofeng Wong, Stephen T. |
author_facet | Yang, Jian Fan, Jing Li, Ying Li, Fuhai Chen, Peikai Fan, Yubo Xia, Xiaofeng Wong, Stephen T. |
author_sort | Yang, Jian |
collection | PubMed |
description | Glioblastoma Multiforme (GBM) cells are highly invasive, infiltrating into the surrounding normal brain tissue, making it impossible to completely eradicate GBM tumors by surgery or radiation. Increasing evidence also shows that these migratory cells are highly resistant to cytotoxic reagents, but decreasing their migratory capability can re-sensitize them to chemotherapy. These evidences suggest that the migratory cell population may serve as a better therapeutic target for more effective treatment of GBM. In order to understand the regulatory mechanism underlying the motile phenotype, we carried out a genome-wide RNAi screen for genes inhibiting the migration of GBM cells. The screening identified a total of twenty-five primary hits; seven of them were confirmed by secondary screening. Further study showed that three of the genes, FLNA, KHSRP and HCFC1, also functioned in vivo, and knocking them down caused multifocal tumor in a mouse model. Interestingly, two genes, KHSRP and HCFC1, were also found to be correlated with the clinical outcome of GBM patients. These two genes have not been previously associated with cell migration. |
format | Online Article Text |
id | pubmed-3625150 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-36251502013-04-16 Genome-Wide RNAi Screening Identifies Genes Inhibiting the Migration of Glioblastoma Cells Yang, Jian Fan, Jing Li, Ying Li, Fuhai Chen, Peikai Fan, Yubo Xia, Xiaofeng Wong, Stephen T. PLoS One Research Article Glioblastoma Multiforme (GBM) cells are highly invasive, infiltrating into the surrounding normal brain tissue, making it impossible to completely eradicate GBM tumors by surgery or radiation. Increasing evidence also shows that these migratory cells are highly resistant to cytotoxic reagents, but decreasing their migratory capability can re-sensitize them to chemotherapy. These evidences suggest that the migratory cell population may serve as a better therapeutic target for more effective treatment of GBM. In order to understand the regulatory mechanism underlying the motile phenotype, we carried out a genome-wide RNAi screen for genes inhibiting the migration of GBM cells. The screening identified a total of twenty-five primary hits; seven of them were confirmed by secondary screening. Further study showed that three of the genes, FLNA, KHSRP and HCFC1, also functioned in vivo, and knocking them down caused multifocal tumor in a mouse model. Interestingly, two genes, KHSRP and HCFC1, were also found to be correlated with the clinical outcome of GBM patients. These two genes have not been previously associated with cell migration. Public Library of Science 2013-04-12 /pmc/articles/PMC3625150/ /pubmed/23593504 http://dx.doi.org/10.1371/journal.pone.0061915 Text en © 2013 Yang et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited. |
spellingShingle | Research Article Yang, Jian Fan, Jing Li, Ying Li, Fuhai Chen, Peikai Fan, Yubo Xia, Xiaofeng Wong, Stephen T. Genome-Wide RNAi Screening Identifies Genes Inhibiting the Migration of Glioblastoma Cells |
title | Genome-Wide RNAi Screening Identifies Genes Inhibiting the Migration of Glioblastoma Cells |
title_full | Genome-Wide RNAi Screening Identifies Genes Inhibiting the Migration of Glioblastoma Cells |
title_fullStr | Genome-Wide RNAi Screening Identifies Genes Inhibiting the Migration of Glioblastoma Cells |
title_full_unstemmed | Genome-Wide RNAi Screening Identifies Genes Inhibiting the Migration of Glioblastoma Cells |
title_short | Genome-Wide RNAi Screening Identifies Genes Inhibiting the Migration of Glioblastoma Cells |
title_sort | genome-wide rnai screening identifies genes inhibiting the migration of glioblastoma cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3625150/ https://www.ncbi.nlm.nih.gov/pubmed/23593504 http://dx.doi.org/10.1371/journal.pone.0061915 |
work_keys_str_mv | AT yangjian genomewidernaiscreeningidentifiesgenesinhibitingthemigrationofglioblastomacells AT fanjing genomewidernaiscreeningidentifiesgenesinhibitingthemigrationofglioblastomacells AT liying genomewidernaiscreeningidentifiesgenesinhibitingthemigrationofglioblastomacells AT lifuhai genomewidernaiscreeningidentifiesgenesinhibitingthemigrationofglioblastomacells AT chenpeikai genomewidernaiscreeningidentifiesgenesinhibitingthemigrationofglioblastomacells AT fanyubo genomewidernaiscreeningidentifiesgenesinhibitingthemigrationofglioblastomacells AT xiaxiaofeng genomewidernaiscreeningidentifiesgenesinhibitingthemigrationofglioblastomacells AT wongstephent genomewidernaiscreeningidentifiesgenesinhibitingthemigrationofglioblastomacells |