Impaired tyrosine phosphorylation of membrane type 1-matrix metalloproteinase reduces tumor cell proliferation in three-dimensional matrices and abrogates tumor growth in mice

被引:38
作者
Nyalendo, Carine [1 ,3 ]
Beaulieu, Edith [1 ]
Sartelet, Herve [2 ]
Michaud, Marisol [1 ,3 ]
Fontaine, Nicolas [1 ]
Gingras, Denis [1 ]
Beliveau, Richard [1 ,3 ]
机构
[1] CHU St Justine, Ctr Cancerol Charles Bruneau, Mol Med Lab, Montreal, PQ H3T 1C5, Canada
[2] CHU St Justine, Dept Pathol, Montreal, PQ H3T 1C5, Canada
[3] Univ Quebec, Ctr Rech Biomed, Montreal, PQ H3C 3P8, Canada
关键词
D O I
10.1093/carcin/bgn159
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Pericellular proteolysis of the extracellular matrix by membrane type 1-matrix metalloproteinase (MT1-MMP) confers tumor cells with the ability to proliferate within three-dimensional (3D) matrices and sustains tumor growth in mice. In this study, we show that in addition to its matrix-degrading activity, phosphorylation of MT1-MMP on its unique tyrosine residue located within its cytoplasmic sequence (Tyr573) may also participate to these processes. Fibrosarcoma cells expressing a proteolytically active but non-phosphorylable mutant of MT1-MMP showed a markedly reduced proliferation rate when embedded within 3D type I collagen matrices, this antiproliferative effect being correlated with arrest in the G(0)/G(1) phase of the cell cycle. Impaired tyrosine phosphorylation of MT1-MMP also inhibits anchorage-independent growth of HT-1080 cells in soft agar as well as their invasion of collagen barriers, two prominent attributes of tumor cells, suggesting a broad inhibitory effect of the MT1-MMP mutant on tumorigenesis. Accordingly, whereas HT-1080 cells formed well-vascularized tumors containing tyrosine-phosphorylated MT1-MMP, tumor growth was completely abolished by expression of the non-phosphorylable MT1-MMP mutant. These findings thus indicate a close co-operation between the matrix-degrading activity of MT1-MMP and tyrosine phosphorylation of its intracellular domain for tumor cell invasion and proliferation and suggest that the targeting of the intracellular signaling pathways leading to tyrosine phosphorylation of MT1-MMP may represent an unexpected alternative strategy for the inhibition of this enzyme.
引用
收藏
页码:1655 / 1664
页数:10
相关论文
共 37 条
[1]   Matrix-dependent proteolysis of surface transglutaminase by membrane-type metalloproteinase regulates cancer cell adhesion and locomotion [J].
Belkin, AM ;
Akimov, SS ;
Zaritskaya, LS ;
Ratnikov, BI ;
Deryugina, EI ;
Strongin, AY .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (21) :18415-18422
[2]   p130Cas as a new regulator of mammary epithelial cell proliferation, survival, and HER2-Neu oncogene-dependent breast tumorigenesis [J].
Cabodi, Sara ;
Tinnirello, Agata ;
Di Stefano, Paola ;
Bisaro, Brigitte ;
Ambrosino, Elena ;
Castellano, Isabella ;
Sapino, Anna ;
Arisio, Riccardo ;
Cavallo, Federica ;
Forni, Guido ;
Glukhova, Marina ;
Silengo, Lorenzo ;
Altruda, Fiorella ;
Turco, Emilia ;
Tarone, Guido ;
Defilippi, Paola .
CANCER RESEARCH, 2006, 66 (09) :4672-4680
[3]   Microassay for the assessment of low levels of hydroxyproline [J].
Creemers, LB ;
Jansen, DC ;
vanVeenReurings, A ;
vandenBos, T ;
Everts, V .
BIOTECHNIQUES, 1997, 22 (04) :656-658
[4]   Tissue inhibitor of metalloproteinases-2 binding to membrane-type 1 matrix metalloproteinase induces MAPK activation and cell growth by a non-proteolytic mechanism [J].
D'Alessio, Silvia ;
Ferrari, Giovanni ;
Cinnante, Karma ;
Scheerer, William ;
Galloway, Aubrey C. ;
Roses, Daniel F. ;
Rozanov, Dmitri V. ;
Remacle, Albert G. ;
Oh, Eok-Soo ;
Shiryaev, Sergey A. ;
Strongin, Alex Y. ;
Pintucci, Giuseppe ;
Mignatti, Paolo .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (01) :87-99
[5]   Membrane-type matrix metalloproteinases 1 and 2 exhibit broad-spectrum proteolytic capacities comparable to many matrix metalloproteinases [J].
d'Ortho, MP ;
Will, H ;
Atkinson, S ;
Butler, G ;
Messent, A ;
Gavrilovic, J ;
Smith, B ;
Timpl, R ;
Zardi, L ;
Murphy, G .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1997, 250 (03) :751-757
[6]   Cancer - Proteases - invasion and more [J].
Edwards, DR ;
Murphy, G .
NATURE, 1998, 394 (6693) :527-528
[7]   New functions for the matrix metalloproteinases in cancer progression [J].
Egeblad, M ;
Werb, Z .
NATURE REVIEWS CANCER, 2002, 2 (03) :161-174
[8]   Cell migration in 3D matrix [J].
Even-Ram, S ;
Yamada, KM .
CURRENT OPINION IN CELL BIOLOGY, 2005, 17 (05) :524-532
[9]   Matrix metalloproteinases in cancer:: from new functions to improved inhibition strategies [J].
Folgueras, AR ;
Pendás, AM ;
Sánchez, LM ;
López-Otín, C .
INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY, 2004, 48 (5-6) :411-424
[10]   Activation of the extracellular signal-regulated protein kinase (ERK) cascade by membrane-type-1 matrix metalloproteinase (MT1-MMP) [J].
Gingras, D ;
Bousquet-Gagnon, N ;
Langlois, S ;
Lachambre, MP ;
Annabi, B ;
Béliveau, R .
FEBS LETTERS, 2001, 507 (02) :231-236