Laminin induces matrix metalloproteinase-9 expression and activation in human cervical cancer cell line (SiHa)

Gargi Maity, Triparna Sen, Amitava Chatterjee

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Purpose: 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. Matrix metalloproteinases (MMP) are a family of metalloproteinases capable of digesting ECM and facilitate cell migration. Binding of ECM to integrins initiates signaling cascades modulating expression and activity of different MMPs. The present study investigates whether laminin-mediated signaling modulates matrix metalloproteinases (MMP) expression and activity in human cervical cancer cell (SiHa). Methods: Western blot, immunocytochemistry, ELISA, zymography, RT-PCR, EMSA and wound-healing assay were used. Results: Culture of SiHa cells on laminin (LN)-coated surface induces MMP-9 expression and activation. Wound-healing assay showed that SiHa cells migrate much faster on laminin-coated surface than that of control. LN-induced MMP-9 expression and activation was appreciably reduced with treatment of extracellular signal-regulated kinase (ERK) inhibitor, phosphatidylinositol-3-kinase (PI-3K) inhibitor and anti-α2 antibody. Phosphorylation of focal adhesion kinase (FAK), ERK, and PI-3K was increased upon LN stimulation. LN induces nuclear translocation of PI-3K and nuclear factor kappa B (NF-κB). LN increases DNA-binding activity of NF-κB and activator protein-1 (AP-1) to MMP-9 promoter. Conclusions: Our findings indicate laminin-induced MMP-9 expression and activation possibly via α2β1 integrin-mediated signaling involving FAK, PI-3K, ERK followed by transcriptional upregulation of MMP-9.

Original languageEnglish
Pages (from-to)347-357
Number of pages11
JournalJournal of Cancer Research and Clinical Oncology
Volume137
Issue number2
DOIs
StatePublished - Feb 2011
Externally publishedYes

Keywords

  • ERK
  • Integrin
  • Laminin
  • MMP-9
  • NF-κB
  • PI-3K

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