Kornberg Lori J
Department of Otolaryngology, University of Florida College of Medicine, Gainesville, Florida 32610, USA.
Anticancer Res. 2005 Nov-Dec;25(6B):4349-56.
Focal adhesion kinase (FAK), which is overexpressed in many human epithelial cancers, regulates cell cycle progression, cellular migration, invasion and survival.
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.
粘着斑激酶（FAK）在许多人类上皮癌中过表达，可调节细胞周期进程、细胞迁移、侵袭和存活。
为了确定抑制FAK活性是否会增强对头颈部区域转化上皮细胞（SCCHN细胞）的药物诱导细胞毒性，用一种导致FAK的显性负性抑制剂FRNK过表达的重组腺病毒转染细胞。结果：当用Ad-FRNK转染SCCHN细胞（SCC25和RPMI 2650）时，FAK的自磷酸化减少，同时FRNK表达大幅增加。Ad-FRNK和细胞毒性药物在降低细胞活力和增加凋亡方面比单独使用Ad-FRNK或单独使用药物更有效。用Ad-FRNK转染还导致培养的SCCHN细胞迁移显著减少。这些结果表明，FAK可能是抗癌治疗的一个良好靶点。
