Induction of cell migration by matrix metalloprotease-2 cleavage of laminin-5.
Structural changes in the extracellular matrix are necessary for cell migration during tissue remodeling and tumor invasion. Specific cleavage of laminin-5 (Ln-5) by matrix metalloprotease-2 (MMP2) was shown to induce migration of breast epithelial cells. MMP2 cleaved the Ln-5 gamma2 subunit at residue 587, exposing a putative cryptic promigratory site on Ln-5 that triggers cell motility. This altered form of Ln-5 is found in tumors and in tissues undergoing remodeling, but not in quiescent tissues. Cleavage of Ln-5 by MMP2 and the resulting activation of the Ln-5 cryptic site may provide new targets for modulation of tumor cell invasion and tissue remodeling.
Giannelli
G
G
Department of Cell Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
Falk-Marzillier
J
J
Schiraldi
O
O
Stetler-Stevenson
W G
WG
Quaranta
V
V
D000818:Animals; D001940:Breast / Q000166:cytology* / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002455:Cell Division; D002460:Cell Line; D002465:Cell Movement; D048429:Cell Size; D017364:Collagenases / Q000378:metabolism; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D005341:Fibrinolysin / Q000378:metabolism; D018093:Gelatinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology; D013876:Thiophenes / Q000494:pharmacology; D000097794:Kalinin
D015815:Cell Adhesion Molecules; D017364:Collagenases; D005341:Fibrinolysin; D018093:Gelatinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases; D010649:Phenylalanine; D011480:Protease Inhibitors; D011993:Recombinant Fusion Proteins; D013876:Thiophenes; D000097794:Kalinin; C080985:batimastat