Lori J Kornberg1. 1. Department of Otolaryngology, University of Florida College of Medicine, Gainesville, Florida 32610, USA. kornblj@ent.ufl.edu
Abstract
BACKGROUND: Focal adhesion kinase (FAK), which is overexpressed in many human epithelial cancers, regulates cell cycle progression, cellular migration, invasion and survival. MATERIALS AND METHODS: In order to determine if inhibiting FAK activity augments drug-induced cytotoxicity in transformed epithelial cells from the head and neck region (SCCHN cells), cells were transfected with a recombinant adenovirus causing overexpression of FRNK a dominant negative inhibitor of FAK Results: When SCCHN cells (SCC25 and RPMI 2650) were transfected with Ad-FRNK there was a decrease in autophosphorylation of FAK, coincident with a large increase in FRNK expression. Ad-FRNK and cytotoxic drugs were more effective in reducing cell viability and increasing apoptosis then Ad-FRNK alone or drugs alone. Transfection with Ad-FRNK also led to substantially decreased migration of cultured SCCHN cells. These results indicate that FAK may be a good target for anticancer therapy.
BACKGROUND:Focal adhesion kinase (FAK), which is overexpressed in many humanepithelial cancers, regulates cell cycle progression, cellular migration, invasion and survival. MATERIALS AND METHODS: In order to determine if inhibiting FAK activity augments drug-induced cytotoxicity in transformed epithelial cells from the head and neck region (SCCHN cells), cells were transfected with a recombinant adenovirus causing overexpression of FRNK a dominant negative inhibitor of FAK Results: When SCCHN cells (SCC25 and RPMI 2650) were transfected with Ad-FRNK there was a decrease in autophosphorylation of FAK, coincident with a large increase in FRNK expression. Ad-FRNK and cytotoxic drugs were more effective in reducing cell viability and increasing apoptosis then Ad-FRNK alone or drugs alone. Transfection with Ad-FRNK also led to substantially decreased migration of cultured SCCHN cells. These results indicate that FAK may be a good target for anticancer therapy.