Silencing of focal adhesion kinase by tumor direct injection of small  interfering RNA decreases in vivo tumor growth.
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.
Tsutsumi
Kae
K
Tsukuba Research Institute, Novartis Pharma, KK, Tsukuba-shi, Ibaraki, Japan.
Yamaura
Takeshi
T
Nakajima
Motowo
M
Honda
Toshiyuki
T
Kasaoka
Tatsuhiko
T
D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007267:Injections; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D034741:RNA, Small Interfering; D051416:Focal Adhesion Protein-Tyrosine Kinases