fibronectin; alternative splicing; Fn-proteinase; migration-stimulating factor; cancer
Abstract :
[en] Like most extracellular matrix (ECM) components, fibronectin (Fn) is proteolyzed generating specific activities. Fibronectin proteinase (Fn-proteinase) represents such a cryptic activity located in the gelatin-binding domain (GBD) of Fn and displays a zinc metalloproteinase activity. The migration-stimulating factor (MSF) is a truncated Fn isoform generated by alternative mRNA splicing and corresponds to the N-terminal part of Fn that comprises the GBD. We show that several human mammary epithelial cells express MSF and constitutively produce Fn-proteinase activity. Furthermore, recombinant M F produced by HEK-293 and MCF-7 cells possesses a constitutive Fn-proteinase activity. Mutating the putative zinc-binding motif, HEXXH, of the protein abolishes its activity thereby demonstrating its specificity. Using PCR, we showed that MSF is barely expressed in normal breast tissues, whereas its expression is significantly increased in tumors. Furthermore, an association between MSF expression and invasive capacity is observed in various breast adenocarcinoma cell lines. Indeed, when stably transfected in non-invasive MCF-7 cells, MSF promotes cell migration in a mechanism mostly dependent on its Fn-proteinase activity. In summary, our study shows that: (i) MSF displays constitutive Fn-proteinase activity; (ii) MSF expression is induced in human breast cancer; and (iff) MSF confers pro-migratory activity that depends mostly on its Fn-proteinase activity. These results suggest that MSF may be involved in tumor progression. (C) 2005 Wiley-Liss, Inc.
Disciplines :
Oncology
Author, co-author :
Houard, X.
Germain, S.
Gervais, M.
Michaud, A.
van den Brule, F.
Foidart, Jean-Michel ; Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique
Noël, Agnès ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Monnot, C.
Corvol, P.
Language :
English
Title :
Migration-stimulating factor displays HEXXH-dependent catalytic activity important for promoting tumor cell migration
Publication date :
01 September 2005
Journal title :
International Journal of Cancer
ISSN :
0020-7136
eISSN :
1097-0215
Publisher :
Wiley Liss, Inc., New York, United States - New York
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