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

• Published in: Cancer biology & therapy Vol. 8; no. 13; pp. 1292 - 1299
• Main Authors: Tsutsumi, Kae, Yamaura, Takeshi, Nakajima, Motowo, Honda, Toshiyuki, Kasaoka, Tatsuhiko
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01-07-2009
• Subjects: Animals; Binding; Biology; Bioscience; Blotting, Western; Calcium; Cancer; Cell; Cell Line, Tumor; Cycle; Female; Focal Adhesion Protein-Tyrosine Kinases - genetics; Focal Adhesion Protein-Tyrosine Kinases - metabolism; HeLa Cells; Humans; Injections; Landes; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasms, Experimental - genetics; Neoplasms, Experimental - pathology; Neoplasms, Experimental - therapy; Organogenesis; Plasmids - administration & dosage; Plasmids - genetics; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Prostatic Neoplasms - therapy; Proteins; RNA Interference; RNA, Small Interfering - genetics; Tumor Burden; Xenograft Model Antitumor Assays - methods
• ISSN: 1538-4047; 1555-8576
• DOI: 10.4161/cbt.8.13.8884

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.