Silencing of focal adhesion kinase by tumor direct injection of small interfering RNA decreases in vivo tumor growth

Abstract

Focal adhesion kinase (FAK) is shown to be frequently correlated with malignancy of the

tumor and poor prognosis of the diseases. Because FAK resides immediately downstream

of the interaction of cell surface adhesion molecules and extracellular matricies, it is

considered to be critical to regulate several cellular processes including growth,

differentiation, adhesion, motility, and apoptosis. However, the studies on the role of FAK

related to cell proliferation have been limited even in vitro. Here, in order to validate the

role of FAK in in vivo tumor formation and proliferation, we employed direct intratumoral

injection of short hairpin RNA (shRNA) targeting FAK with cationic liposome. Using

shRNAs targeting FAK selected from the constructed shRNA library for FAK and by

optimization of in vivo delivery conditions, we demonstrated different patterns of the

association of FAK inhibition with in vivo tumor formation/proliferation inhibition in two

models, PC3M heterotopic xenograft and 4T1 orthotopic syngraft models. These

observations indicated that the roles of FAK in tumorigenesis are different among the

tumor species. In addition, we showed that ERK is the critical MAP kinase in the signaling

pathway down stream of FAK in in vivo proliferation of 4T1 tumor cells.