TY - JOUR
T1 - Genome-Wide RNAi Screening Identifies Genes Inhibiting the Migration of Glioblastoma Cells
AU - Yang, Jian
AU - Fan, Jing
AU - Li, Ying
AU - Li, Fuhai
AU - Chen, Peikai
AU - Fan, Yubo
AU - Xia, Xiaofeng
AU - Wong, Stephen T.
N1 - Funding Information:
The authors wish to acknowledge the contributions of several individuals at GTRI to the software and models described in this paper. Much of the GTVISIT code in its present form is the work of Bruce Crawford. The implementation of the IRMA code used in this study is due to Keith Johnson. Nick Faust was instrumental in developing the gridded feature database for the village scene. The implementation of Gardner's algorithms for cloud backgrounds was due to Greg Galloway. Much of the effort in the calculation of the radiances for the scene elements was performed by Anthony Meyers, Lisa Meyers, Greg Rohling, and John Growdon. The research effort leading to the imagery presented in this paper was performed under Air Force Contract No. F09603-85-G-3104.
PY - 2013/4/12
Y1 - 2013/4/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84876079529&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0061915
DO - 10.1371/journal.pone.0061915
M3 - Article
C2 - 23593504
AN - SCOPUS:84876079529
SN - 1932-6203
VL - 8
JO - PloS one
JF - PloS one
IS - 4
M1 - e61915
ER -