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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Syndecan-1 modulates β-integrin-dependent and interleukin-6-dependent functions in breast cancer cell adhesion, migration, and resistance to irradiation
FEBS Journal, Volume 280, No. 10, Year 2013
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Description
Syndecan-1 is a cell surface heparan sulfate proteoglycan with various biological functions relevant to tumor progression and inflammation, including cell-cell adhesion, cell-matrix interaction, and cytokine signaling driving cell proliferation and motility. Syndecan-1 is a prognostic factor in breast cancer, and has a predicitive value for neodadjuvant chemotherapy. It is still poorly understood how syndecan-1 integrates matrix-dependent and cytokine-dependent signaling processes in the tumor microenvironment. Here, we evaluated the potential role of syndecan-1 in modulating matrix-dependent breast cancer cell migration in the presence of interleukin-6, and its potential involvement in resistance to irradiation in vitro. MDA-MB-231 breast cancer cells were transiently transfected with syndecan-1 small interfering RNA or control reagents, and this was followed by stimulation with interleukin-6 or irradiation. Cellular responses were monitored by adhesion, migration and colony formation assays, as well as analysis of cell signaling. Syndecan-1 depletion increased cell adhesion to fibronectin. Increased migration on fibronectin was significantly suppressed by interleukin-6, and GRGDSP peptides inhibited both adhesion and migration. Interleukin-6-induced activation of focal adhesion kinase and reduction of constitutive nuclear factor kappaB signaling were decreased in syndecan-1-deficient cells. Focal adhesion kinase hyperactivation in syndecan-1-depleted cells was associated with dramatically reduced radiation sensitivity. We conclude that loss of syndecan-1 leads to enhanced activation of β1-integrins and focal adhesion kinase, thus increasing breast cancer cell adhesion, migration, and resistance to irradiation. Syndecan-1 deficiency also attenuates the modulatory effect of the inflammatory microenvironment constituent interleukin-6 on cancer cell migration. The cell surface heparan sulfate proteoglycan syndecan-1 modulates breast cancer cell adhesion to fibronectin in an integrin-dependent manner, while increased cell motility in syndecan-1-deficient cells depends on both integrins and IL-6. Increased activation of FAK in the absence of Sdc-1 is associated with increased resistance to irradiation. IL-6-dependent modulation of FAK and NF- Cyrillic small letter kaB are inhibited by syndecan-1 depletion. © 2013 The Authors Journal compilation © 2013 FEBS.
Authors & Co-Authors
Hassan, Hebatallah H.M.
Germany, Munster
Universitätsklinikum Münster
Egypt, Giza
Faculty of Science
Grève, Burkhard
Germany, Munster
Universitätsklinikum Münster
Pavão, M. S.
Brazil, Rio de Janeiro
Universidade Federal do Rio de Janeiro
Kiesel, Ludwig
Germany, Munster
Universitätsklinikum Münster
Ibrahim, Sherif Abdelaziz
Germany, Munster
Universitätsklinikum Münster
Egypt, Giza
Faculty of Science
Götte, Martin
Germany, Munster
Universitätsklinikum Münster
Statistics
Citations: 103
Authors: 6
Affiliations: 3
Identifiers
Doi:
10.1111/febs.12111
ISSN:
1742464X
e-ISSN:
17424658
Research Areas
Cancer