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

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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.

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Acknowledgments

This work was supported by the Department of Biotechnology (DBT), Government of India (Sanction No. BT/PR3201/MED/30/643/2011). We thank Dr. Hakon Leffler, Lund University, Sweden, for the expression vector for rhGalectin-3, National Centre for Cell Science, Pune, India for the melanoma cell line and Mr. D. S. Chavan and Mr. A. M. Pawar for technical help. We acknowledge the Council for Scientific and Industrial Research (CSIR) and DBT for providing fellowship to Mr. MC Dange and Mr. AK Agarwal from CSIR and ACTREC, Government of India.

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

    Manohar C. Dange, Akhil Kumar Agarwal & Rajiv D. Kalraiya

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  1. Manohar C. Dange
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  2. Akhil Kumar Agarwal
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Correspondence to Rajiv D. Kalraiya.

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Dange, M.C., Agarwal, A.K. & Kalraiya, R.D. Extracellular galectin-3 induces MMP9 expression by activating p38 MAPK pathway via lysosome-associated membrane protein-1 (LAMP1). Mol Cell Biochem 404, 79–86 (2015). https://doi.org/10.1007/s11010-015-2367-5

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