Extracellular galectin-3 induces MMP9 expression by activating p38 MAPK pathway via lysosome-associated membrane protein-1 (LAMP1).
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.
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
MC
Dange
Akhil Kumar
AK
Agarwal
Rajiv D
RD
Kalraiya
D000818:Animals; D045744:Cell Line, Tumor; D037502:Galectin 3 / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D052118:Lysosomal-Associated Membrane Protein 1 / Q000096:biosynthesis* / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D008546:Melanoma, Experimental / Q000235:genetics / Q000473:pathology; D051379:Mice; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis* / Q000235:genetics
D037502:Galectin 3; D052118:Lysosomal-Associated Membrane Protein 1; D048051:p38 Mitogen-Activated Protein Kinases; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9