title: Focal adhesion kinase and p53 synergistically decrease neuroblastoma cell survival.
abstract: Neuroblastoma is the most common extracranial solid tumor of childhood and is responsible for over 15% of pediatric cancer deaths. Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that is important in many facets of neuroblastoma tumor development and progression. The p53 oncogene, although wild type in most neuroblastomas, lacks significant function as a tumor suppressor in these tumors. Recent reports have found that FAK and p53 interact in some tumor types. We have hypothesized FAK and p53 coordinately control each other's expression and also interact in neuroblastoma. In the present study, we showed that not only do FAK and p53 interact but each one controls the expression of the other. In addition, we also examined the effects of FAK inhibition combined with p53 activation in neuroblastoma and showed that these two, in combination, had a synergistic effect on neuroblastoma cell survival. The findings from this present study help to further our understanding of the regulation of neuroblastoma tumorigenesis and may provide novel therapeutic strategies and targets for neuroblastoma and other pediatric solid tumors.
authors: Department of Surgery, University of Alabama, Birmingham, Alabama.
authors: Lauren A
authors: LA
authors: Gillory
authors: Department of Surgery, University of Alabama, Birmingham, Alabama.
authors: Jerry E
authors: JE
authors: Stewart
authors: Department of Surgery, University of Alabama, Birmingham, Alabama.
authors: Michael L
authors: ML
authors: Megison
authors: Department of Surgery, University of Alabama, Birmingham, Alabama.
authors: Alicia M
authors: AM
authors: Waters
authors: Department of Surgery, University of Alabama, Birmingham, Alabama. Electronic address: elizabeth.beierle@childrensal.org.
authors: Elizabeth A
authors: EA
authors: Beierle
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D006801:Humans; D009447:Neuroblastoma / Q000201:enzymology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; D051416:Focal Adhesion Protein-Tyrosine Kinases
keywords: FAK; Neuroblastoma; SH-EP; WAC(2); p53