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Extracellular galectin-3 induces MMP9 expression by activating p38 MAPK pathway via lysosome-associated membrane

Manohar C Dange1, Akhil Kumar Agarwal, Rajiv D Kalraiya

  • 1Kalraiya Lab, KS 131, Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre, Sector 22, Kharghar, Navi Mumbai, 410210, India.

Molecular and Cellular Biochemistry
|March 6, 2015
PubMed

Insights

Extracellular galectin-3 induces matrix metalloproteinase-9 (MMP9) at the transcript level, a process mediated by poly-N-acetyllactosamine (polyLacNAc) on cell surfaces. This induction occurs via the p38 MAP-kinase pathway, with lysosome-associated membrane protein-1 (LAMP1) playing a key role.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • Matrix metalloproteinases (MMPs) are crucial for matrix remodeling, influencing cancer invasion and metastasis.
  • Extracellular galectin-3 is known to stimulate the secretion of MMP9.

Purpose of the Study:

  • To elucidate the mechanism by which galectin-3 induces MMP9 expression.
  • To investigate the role of cell surface molecules and signaling pathways in galectin-3-mediated MMP9 induction.

Main Methods:

  • Analysis of MMP9 transcript levels in response to galectin-3.
  • Investigation of the role of poly-N-acetyllactosamine (polyLacNAc) and lysosome-associated membrane protein-1 (LAMP1).
  • Utilizing signaling pathway inhibitors, specifically targeting the p38 MAP-kinase pathway.
  • Employing melanoma cell clones with shRNAs targeting LAMP1.

Main Results:

  • Galectin-3 induces MMP9 expression at the transcript level.
  • This induction is dependent on the surface levels of poly-N-acetyllactosamine (polyLacNAc).
  • The p38 MAP-kinase pathway is essential for galectin-3-induced MMP9 expression.
  • Surface LAMP1 acts as a key mediator in galectin-3-induced MMP9 expression via the p38 MAPK pathway.

Conclusions:

  • Galectin-3-induced MMP9 expression in melanoma cells is mediated by surface polyLacNAc and LAMP1.
  • The p38 MAPK signaling pathway is a critical component of this induction mechanism.
  • Understanding this pathway provides insights into targeting cancer invasion and metastasis.

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