title: The role of Src family kinases in growth and migration of glioma stem cells.
abstract: Src family kinases (SFKs) are highly expressed and active in clinical glioblastoma multiforme (GBM) specimens. SFKs inhibitors have been demonstrated to inhibit proliferation and migration of glioma cells. However, the role of SFKs in glioma stem cells (GSCs), which are important for treatment resistance and recurrence, has not been reported. Here, we examined the expression pattern of individual members of SFKs and their functional role in CD133⁺ GSCs in comparison to primary glioma cells. We found that Fyn, c-Src and Yes were robustly expressed in GSCs while Lck was absent. Knockdown of c-Src, Yes or treatment with the SFK inhibitor dasatinib inhibited the migration of GSCs, but had no impact on their growth or self-renewal. These results suggest that SFKs represent an effective target for GSC migration but not for their growth.
authors.affiliation: Division of Neuro-Oncology, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294-3410, USA.
authors.forename: Xiaosi
authors.initials: X
authors.lastname: Han
authors.affiliation: Division of Neuro-Oncology, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294-3410, USA.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Division of Neuro-Oncology, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294-3410, USA.
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Yang
authors.affiliation: Division of Neuro-Oncology, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294-3410, USA.
authors.forename: Crystal G
authors.initials: CG
authors.lastname: Wheeler
authors.affiliation: Division of Neurosurgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294-3410, USA.
authors.forename: Catherine P
authors.initials: CP
authors.lastname: Langford
authors.affiliation: Division of Neuro-Oncology, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294-3410, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Wu
authors.affiliation: Division of Neuro-Oncology, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294-3410, USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: Filippova
authors.affiliation: Division of Hematology/Oncology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35294-3410, USA.
authors.forename: Gregory K
authors.initials: GK
authors.lastname: Friedman
authors.affiliation: Division of Pulmonary Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294-3410, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ding
authors.affiliation: Division of Neuro-Oncology, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294-3410, USA.
authors.forename: Hassan M
authors.initials: HM
authors.lastname: Fathallah-Shaykh
authors.affiliation: Division of Neurosurgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294-3410, USA.
authors.forename: G Yancey
authors.initials: GY
authors.lastname: Gillespie
authors.affiliation: Division of Neuro-Oncology, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294-3410, USA.
authors.forename: L Burt
authors.initials: LB
authors.lastname: Nabors
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000081247:CSK Tyrosine-Protein Kinase; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D000069439:Dasatinib; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D009374:Neoplasms, Experimental; D014411:Neoplastic Stem Cells / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism; D051575:Proto-Oncogene Proteins c-yes / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D015854:Up-Regulation; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000081247:CSK Tyrosine-Protein Kinase; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn; D051575:Proto-Oncogene Proteins c-yes; C489834:YES1 protein, human; D019061:src-Family Kinases; C000631346:CSK protein, human; D000069439:Dasatinib