Focal adhesion kinase regulates syndecan-2-mediated tumorigenic activity of HT1080 fibrosarcoma cells

Haein Park, Innoc Han, Ho Jeong Kwon, Eok Soo Oh

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)9899-9905
Number of pages7
JournalCancer Research
Volume65
Issue number21
DOIs
Publication statusPublished - 2005 Nov 1

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Syndecan-2
Focal Adhesion Protein-Tyrosine Kinases
Fibrosarcoma
Phosphatidylinositol 3-Kinase
Cell Movement
Lymphoma
Colon
Cell-Matrix Junctions
Neoplasm Metastasis
Carcinoma
Heparan Sulfate Proteoglycans
Growth
Cell Adhesion
Cell Communication
Sarcoma
Small Interfering RNA
Transcriptional Activation
Extracellular Matrix

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

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abstract = "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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Focal adhesion kinase regulates syndecan-2-mediated tumorigenic activity of HT1080 fibrosarcoma cells. / Park, Haein; Han, Innoc; Kwon, Ho Jeong; Oh, Eok Soo.

In: Cancer Research, Vol. 65, No. 21, 01.11.2005, p. 9899-9905.

Research output: Contribution to journalArticle

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AU - Han, Innoc

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