title: Genome-wide RNAi screening identifies genes inhibiting the migration of glioblastoma cells.
abstract: 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.
authors.affiliation: Department of Systems Medicine and Bioengineering, The Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, Texas, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.forename: Jing
authors.initials: J
authors.lastname: Fan
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Fuhai
authors.initials: F
authors.lastname: Li
authors.forename: Peikai
authors.initials: P
authors.lastname: Chen
authors.forename: Yubo
authors.initials: Y
authors.lastname: Fan
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Xia
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Wong
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D016923:Cell Death / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D052138:Genes, Neoplasm / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D051379:Mice; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015203:Reproducibility of Results; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D034741:RNA, Small Interfering