FAK silencing inhibits leukemogenesis in BCR/ABL-transformed hematopoietic cells.
Focal adhesion kinase (FAK) is constitutively activated and tyrosine phosphorylated in BCR/ABL-transformed hematopoietic cells, but the role it plays during leukemogenesis remains unclear. Here, we examined the effects of RNA interference-mediated FAK silencing on leukemogenesis induced by a BCR/ABL-transformed cell line. Transduction of BCR/ABL-BaF3 cells with FAK shRNA inhibited FAK expression and reduced STAT5 phosphorylation, but induced caspase-3 activation. In vitro studies showed that treatment with FAK shRNA resulted in impaired cell proliferation and colony formation, while increasing cell apoptosis. Mice that received transplants of BCR/ABL-BaF3 cells with FAK shRNA displayed significantly prolonged survival time and diminished leukemia progression. In addition, FAK silencing enhanced in vitro and in vivo efficacy of ABL tyrosine kinase inhibitor imatinib in BCR/ABL-BaF3 cells. Our results suggest that FAK is critical for leukemogenesis and might be a potential target for leukemia therapy.
Department of Pathology, Joint Program in Transfusion Medicine, Children's Hospital Boston, Karp Research Building, Room 10217, One Blackfan Circle, Boston, MA 02115, USA. yi.le@med.navy.mil
Yi
Y
Le
Luhong
L
Xu
Jiayun
J
Lu
Jianpei
J
Fang
Valentina
V
Nardi
Li
L
Chai
Leslie E
LE
Silberstein
D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D016044:Fusion Proteins, bcr-abl / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D010766:Phosphorylation; D034622:RNA Interference; D050799:STAT5 Transcription Factor / Q000378:metabolism
D014408:Biomarkers, Tumor; D050799:STAT5 Transcription Factor; D051416:Focal Adhesion Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl