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Focal Adhesion Kinase Regulates Syndecan-2–Mediated Tumorigenic Activity of HT1080 Fibrosarcoma Cells

¹ Department of Life Science, Division of Molecular Life Sciences and Center for Cell Signaling Research, Ewha Womans University; ² Department of Bioscience and Biotechnology, Institute of Bioscience, Sejong University, Seoul, Korea; and ³ Department of Physiology and Biophysics, Inha University, Incheon, Korea

Requests for reprints: Eok-Soo Oh, Center for Cell Signaling Research, Ewha Womans University, Daehyun-dong, Seodaemoon-Gu, Seoul 120-750, Korea. Phone: 82-2-3277-3761; Fax: 82-2-3277-3760; E-mail: OhES{at}ewha.ac.kr.

Expression of syndecan-2, a transmembrane heparan sulfate proteoglycan, is crucial for the tumorigenic activity in colon carcinoma cells. However, despite the high-level expression of syndecan-2 in mesenchymal cells, few studies have addressed the function of syndecan-2 in sarcoma cells. In HT1080 fibrosarcoma cells, we found that syndecan-2 regulated migration, invasion into Matrigel, and anchorage-independent growth but not cell-extracellular matrix adhesion or proliferation, suggesting that syndecan-2 plays different functional roles in fibrosarcoma and colon carcinoma cells. Consistent with the increased cell migration/invasion of syndecan-2–overexpressing HT1080 cells, syndecan-2 overexpression increased phosphorylation and interaction of focal adhesion kinase (FAK) and phosphatidylinositol 3-kinase (PI3K), membrane localization of T-lymphoma invasion and metastasis gene-1 (Tiam-1), and activation of Rac. Syndecan-2–mediated cell migration/invasion of HT1080 cells was diminished when (a) cells were cotransfected with nonphosphorylatable mutant FAK Y397F or with other FAK mutants lacking PI3K interactions, (b) cells were treated with a specific PI3K inhibitor, or (c) levels of Tiam-1 were knocked down with small interfering RNAs. Furthermore, expression of several FAK mutants inhibited syndecan-2–mediated enhancement of anchorage-independent growth in HT1080 cells. Taken together, these data suggest that syndecan-2 regulates the tumorigenic activities of HT1080 fibrosarcoma cells and that FAK is a key regulator of syndecan-2–mediated tumorigenic activities.

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