Focal adhesion kinase is activated in invading fibrosarcoma cells and regulates metastasis

Masuo Hanada, Kazuhiro Tanaka, Yoshihiro Matsumoto, Fumihiko Nakatani, Riku Sakimura, Tomoya Matsunobu, Xu Li, Takamitsu Okada, Tomoyuki Nakamura, Minoru Takasaki, Yukihide Iwamoto

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that is overexpressed in several human cancers, and induces survival, proliferation and motility of cells in culture. Phosphorylation of FAK has been studied extensively in vitro, but little is known about its regulation during tumor invasion in vivo. In the current study, green fluorescent protein (GFP) was expressed stably in an invasive murine fibrosarcoma cell line for the purpose of discrimination between tumor and normal cells. Under fluorescence microscopy, the tumor was highly fluorescent, and the margin between the tumor and normal tissue was clearly demarcated. Using this invasion model, we showed localization of pY397-FAK expression in the infiltrative edge of tumors. We reproduced local invasion in vivo using a tumor tissue culture method in a three dimensional collagen gel. Phosphorylation of FAK is also upregulated in invading fibrosarcoma cells under in vitro conditions. Expression of the FAK C-terminal domain termed FRNK (FAK-related non-kinase) in 2472 cells decreased FAK phosphorylation without changing total FAK levels. FRNK inhibited the motility of 2472 cells, and reduced invasion in vitro. Although FRNK did not affect cell growth, it inhibited experimental metastases in syngenic mice. These results demonstrate that the phosphorylation of FAK might be specifically upregulated in invading fibrosarcoma cells and regulate their invasion and metastasis.

Original languageEnglish
Pages (from-to)485-494
Number of pages10
JournalClinical and Experimental Metastasis
Volume22
Issue number6
DOIs
Publication statusPublished - Nov 1 2005

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Focal adhesion kinase is activated in invading fibrosarcoma cells and regulates metastasis'. Together they form a unique fingerprint.

  • Cite this

    Hanada, M., Tanaka, K., Matsumoto, Y., Nakatani, F., Sakimura, R., Matsunobu, T., Li, X., Okada, T., Nakamura, T., Takasaki, M., & Iwamoto, Y. (2005). Focal adhesion kinase is activated in invading fibrosarcoma cells and regulates metastasis. Clinical and Experimental Metastasis, 22(6), 485-494. https://doi.org/10.1007/s10585-005-3733-6