title: Inhibition of focal adhesion kinase and src increases detachment and apoptosis in human neuroblastoma cell lines.
abstract: 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.
authors.affiliation: Department of Surgery, University of Alabama, Birmingham, Alabama 35233, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Beierle
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Ma
authors.forename: Angelica
authors.initials: A
authors.lastname: Trujillo
authors.forename: Elena V
authors.initials: EV
authors.lastname: Kurenova
authors.forename: William G
authors.initials: WG
authors.lastname: Cance
authors.forename: Vita M
authors.initials: VM
authors.lastname: Golubovskaya
mesh_terms: 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
chemical_list: 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)