Fibronectin–integrin mediated signaling in human cervical cancer cells (SiHa)
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Interaction between cell surface integrin receptors and extracellular matrix (ECM) components plays an important role in cell survival, proliferation, and migration, including tumor development and invasion of tumor cells. Matrix metalloproteinases (MMPs) are a family of metalloproteinases capable of digesting ECM components and are important molecules for cell migration. Binding of ECM to integrins initiates cascades of cell signaling events modulating expression and activity of different MMPs. The aim of this study is to investigate fibronectin–integrin-mediated signaling and modulation of MMPs. Our findings indicated that culture of human cervical cancer cell (SiHa) on fibronectin-coated surface perhaps sends signals via fibronectin–integrin-mediated signaling pathways recruiting focal adhesion kinase (FAK) extracellular signal regulated kinase (ERK), phosphatidyl inositol 3 kinase (PI-3K), integrin-linked kinase (ILK), nuclear factor-kappa B (NF-κB), and modulates expression and activation of mainly pro-MMP-9, and moderately pro-MMP-2 in serum-free culture medium.
KeywordsIntegrin α5β1 Fibronectin SiHa MMP-9 ERK PI-3K
We acknowledge the financial support and inspiration received from Dr. Jaydip Biswas, Director, CNCI, and the financial support from Department of Science and Technology, New Delhi (Grant No. SR/SO/HS-59/2004).
- 12.Hofmann UB, Westphal JR, Van Kraats AA et al (2000) Expression of integrin alpha (v) beta (3) correlates with activation of membrane-type matrix metalloproteinase-1 (MT1-MMP) and matrix metalloproteinase-2 (MMP-2) in human melanoma cells in vitro and in vivo. Int J Cancer 87:12–19CrossRefPubMedGoogle Scholar
- 13.Johansson S, Svineng G, Wennerberg K et al (1997) Fibronectin–integrin interactions. Front Biosci 2:126–146Google Scholar
- 20.Han S, Ritzenthaler JD, Sitaraman SV et al (2006) Fibronectin increases matrix metalloproteinase 9 expression through activation of c-Fos via extracellular-regulated kinase and phosphatidylinositol 3-kinase pathways in human lung carcinoma cells. J Biol Chem 281:29614–29624CrossRefPubMedGoogle Scholar
- 24.Esparza J, Vilardell C, Calvo J et al (1999) Fibronectin upregulates gelatinase B (MMP-9) and induces coordinated expression of gelatinase A (MMP-2) and its activator MT1-MMP (MMP-14) by human T lymphocyte cell lines. A process repressed through RAS/MAP kinase signaling pathways. Blood 94:2754–2766PubMedGoogle Scholar
- 28.Chattopadhaya N, Mitra A, Frei E et al (2001) Human cervical tumor cell (SiHa) surface alphavbeta3 integrin receptor has associated matrix metalloproteinase (MMP-2) activity. J Cancer Res Clin Oncol 127:653–658Google Scholar
- 34.Chakrobarty J, Mitra A, Banerji A et al (2006) Culture of human fibrosarcoma HT-1080 cells in presence of fibronectin activates MMP-2. J Environ Pathol Toxicol Oncol 25:667–677Google Scholar
- 42.Kwon GT, Cho HJ, Chung WY et al. (2009) Isoliquiritigenin inhibits migration and invasion of prostate cancer cells: possible mediation by decreased JNK/AP-1 signaling. J Nutr Biochem 20(9):663–676Google Scholar
- 46.Farina AR, Tacconelli A, Vacca A et al (1999) Transcriptional up-regulation of matrix metalloproteinase-9 expression during spontaneous epithelial to neuroblast phenotype conversion by SK-N-SH neuroblastoma cells, involved in enhanced invasivity, depends upon GT-box and nuclear factor kappa B elements. Cell Growth Differ 10:353–367PubMedGoogle Scholar