Inhibition of focal adhesion kinase and src increases detachment and apoptosis in human neuroblastoma cell lines.
Neuroblastoma is the most common extracranial solid tumor of childhood. Focal adhesion kinase (FAK) is an intracellular kinase that is overexpressed in a number of human tumors including neuroblastoma, and regulates both cellular adhesion and survival. We have studied the effects of FAK inhibition upon neuroblastoma using adenovirus-containing FAK-CD (AdFAK-CD). Utilizing an isogenic MYCN+/MYCN- neuroblastoma cell line, we found that the MYCN+ cells are more sensitive to FAK inhibition with AdFAK-CD than their MYCN negative counterparts. In addition, we have shown that phosphorylation of Src is increased in the untreated isogenic MYCN- neuroblastoma cells, and that the decreased sensitivity of the MYCN- neuroblastoma cells to FAK inhibition with AdFAK-CD is abrogated by the addition of the Src family kinase inhibitor, PP2. The results of the current study suggest that both FAK and Src play a role in protecting neuroblastoma cells from apoptosis, and that dual inhibition of these kinases may be important when designing therapeutic interventions for this tumor.
Beierle
Elizabeth A
EA
Department of Surgery, University of Alabama, Birmingham, Alabama 35233, USA.
Ma
Xiaojie
X
Trujillo
Angelica
A
Kurenova
Elena V
EV
Cance
William G
WG
Golubovskaya
Vita M
VM
D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D005434:Flow Cytometry; D051417:Focal Adhesion Kinase 1 / Q000037:antagonists & inhibitors*; D016259:Genes, myc; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D016392:Proto-Oncogene Proteins pp60(c-src)