Tumor growth inhibition by synthetic and expressed siRNA targeting focal adhesion kinase

  • Authors:
    • Kae Tsutsumi
    • Tatsuhiko Kasaoka
    • Hyi-Man Park
    • Hiroko Nishiyama
    • Motowo Nakajima
    • Toshiyuki Honda
  • View Affiliations

  • Published online on: July 1, 2008     https://doi.org/10.3892/ijo.33.1.215
  • Pages: 215-224
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Abstract

Focal adhesion kinase (FAK) was first identified as a viral Src substrate, and substantial experimental data have significantly correlated the elevated FAK expression in human tumor cells with an increased cell adhesion and invasion potential. However, studies investigating the role of FAK in cell proliferation have been limited. Recently, a technique known as RNA interference (RNAi) was successfully adapted to mammalian cells to decrease specifically the expression of targeted cellular genes. In this study, we investigated the role of FAK in cell proliferation, adhesion, and migration by using small interfering RNA (siRNA) technique. Firstly, we constructed a plasmid library expressing short hairpin RNAs (shRNAs) targeting FAK and selected clones substantially suppressing FAK expression in HeLa and HT1080 cells. We then studied the function of FAK in the highly invasive human prostate cancer cell line, PC3M, and mouse breast cancer cell line 4T1, by using selected shRNA clones (#40 and #42) and siRNAs chemically synthesized following the target sequences of #40 and #42. We demonstrated that the decrease of FAK protein expression by treatment with shRNA/siRNA targeting FAK inhibited cell adhesion on a fibronectin/laminin-coated plate, cell migration in a haptotactic migration assay, and cell proliferation in vitro. Furthermore, it suppressed tumor growth in vivo in heterotopic/orthotopic mice models. These results support our hypothesis that FAK plays a crucial role in tumor formation and growth in vivo by regulation of cell adhesion and proliferation by FAK-dependent signals.

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July 2008
Volume 33 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Tsutsumi K, Kasaoka T, Park H, Nishiyama H, Nakajima M and Honda T: Tumor growth inhibition by synthetic and expressed siRNA targeting focal adhesion kinase. Int J Oncol 33: 215-224, 2008.
APA
Tsutsumi, K., Kasaoka, T., Park, H., Nishiyama, H., Nakajima, M., & Honda, T. (2008). Tumor growth inhibition by synthetic and expressed siRNA targeting focal adhesion kinase. International Journal of Oncology, 33, 215-224. https://doi.org/10.3892/ijo.33.1.215
MLA
Tsutsumi, K., Kasaoka, T., Park, H., Nishiyama, H., Nakajima, M., Honda, T."Tumor growth inhibition by synthetic and expressed siRNA targeting focal adhesion kinase". International Journal of Oncology 33.1 (2008): 215-224.
Chicago
Tsutsumi, K., Kasaoka, T., Park, H., Nishiyama, H., Nakajima, M., Honda, T."Tumor growth inhibition by synthetic and expressed siRNA targeting focal adhesion kinase". International Journal of Oncology 33, no. 1 (2008): 215-224. https://doi.org/10.3892/ijo.33.1.215