Extracellular galectin-3 induces MMP9 expression by activating p38 MAPK pathway via lysosome-associated membrane protein-1 (LAMP1)

Mol Cell Biochem. 2015 Jun;404(1-2):79-86. doi: 10.1007/s11010-015-2367-5. Epub 2015 Mar 5.

Abstract

Matrix metalloproteinases (MMPs) play a key role in matrix remodelling and thus invasion and metastasis. Extracellular galectin-3 has been shown to induce MMP9 secretion. Here, we demonstrate that galectin-3 induces MMP9 at transcript level and it is dependent on the surface levels of poly-N-acetyllactosamine (polyLacNAc). By employing signalling pathway inhibitors, MMP9 expression was shown to be induced via p38 MAP-kinase pathway. Using clones of melanoma cells expressing shRNAs to lysosome-associated membrane protein-1 (LAMP1), a major carrier of polyLacNAc, surface LAMP1 was demonstrated to serve as one of the key mediators of galectin-3-induced MMP9 expression via p38 MAPK pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Galectin 3 / biosynthesis*
  • Galectin 3 / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lysosomal-Associated Membrane Protein 1 / biosynthesis*
  • Lysosomal-Associated Membrane Protein 1 / genetics
  • MAP Kinase Signaling System / genetics
  • Matrix Metalloproteinase 9 / biosynthesis*
  • Matrix Metalloproteinase 9 / genetics
  • Melanoma, Experimental / genetics
  • Melanoma, Experimental / pathology
  • Mice
  • p38 Mitogen-Activated Protein Kinases / biosynthesis*
  • p38 Mitogen-Activated Protein Kinases / genetics

Substances

  • Galectin 3
  • Lysosomal-Associated Membrane Protein 1
  • p38 Mitogen-Activated Protein Kinases
  • MMP9 protein, human
  • Matrix Metalloproteinase 9