Inhibition of focal adhesion kinase and Src increases detachment and apoptosis in human neuroblastoma cell lines

Academic Article

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. © 2009 Wiley-Liss, Inc.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Beierle EA; Ma X; Trujillo A; Kurenova EV; Cance WG; Golubovskaya VM
  • Start Page

  • 224
  • End Page

  • 234
  • Volume

  • 49
  • Issue

  • 3