Activation of the extracellular signal-regulated protein kinase (ERK) cascade by membrane-type-1 matrix metalloproteinase (MT1-MMP)

• Published in: FEBS letters Vol. 507; no. 2; pp. 231 - 236
• Main Authors: Gingras, Denis, Bousquet-Gagnon, Nathalie, Langlois, Stéphanie, Lachambre, Marie-Paule, Annabi, Borhane, Béliveau, Richard
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 26.10.2001
• Subjects: Animals; Cell Movement; Cercopithecus aethiops; COS Cells; Enzyme Activation; ERK, extracellular signal-regulated protein kinase; Extracellular Matrix - metabolism; Extracellular signal-regulated protein kinase; Gene Expression; Humans; MAP Kinase Signaling System; Matrix Metalloproteinases, Membrane-Associated; Membrane-type-1 matrix metalloproteinase; Metalloendopeptidases - genetics; Metalloendopeptidases - metabolism; Migration; Mitogen-Activated Protein Kinases - metabolism; MMP, matrix metalloproteinase; MT-MMP, membrane-type matrix metalloproteinase; Signal transduction; TIMP, tissue inhibitor of matrix metalloproteinase; Tumor Cells, Cultured; Signal transduction; Extracellular signal-regulated protein kinase; TIMP, tissue inhibitor of matrix metalloproteinase; Migration; MT-MMP, membrane-type matrix metalloproteinase; ERK, extracellular signal-regulated protein kinase; MMP, matrix metalloproteinase; Membrane-type-1 matrix metalloproteinase
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(01)02985-4

The mechanisms underlying membrane-type-1 matrix metalloproteinase (MT1-MMP)-dependent induction of cell migration were investigated. Overexpression of MT1-MMP induced a marked increase in cell migration, this increase being dependent on the presence of the cytoplasmic domain of the protein. MT1-MMP-dependent migration was inhibited by a mitogen-activated protein kinase kinase 1 inhibitor, suggesting the involvement of the extracellular signal-regulated protein kinase (ERK) cascade in the induction of migration. Accordingly, MT1-MMP overexpression induced the activation of ERK, this process being also dependent on the presence of its cytoplasmic domain. MT1-MMP-induced activation of both migration and ERK required the catalytic activity of the enzyme as well as attachment of the cells to matrix proteins. The MT1-MMP-dependent activation of ERK was correlated with the activation of transcription through the serum response element, whereas other promoters were unaffected. Taken together, these results indicate that MT1-MMP trigger important changes in cellular signal transduction events, leading to cell migration and to gene transcription, and that these signals possibly originate from the cytoplasmic domain of the protein.