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SUMMARY:Temporal and spatial regulation of cell surface proteinase\, MT1-M
 MP: an essential mechanism for cellular invasion - Dr. Yoshifumi Itoh\, Ke
 nnedy Institute\, Imperial College London
DTSTART:20100113T123000Z
DTEND:20100113T133000Z
UID:TALK21898@talks.cam.ac.uk
CONTACT:Prof. Jim Kaufman
DESCRIPTION:The long-term goal of the research in our group is to understa
 nd the mechanism of cell migration in tissue. In particular\, we are study
 ing one of the key cell surface proteinases\, MT1-MMP\, during cell migrat
 ion.  ECM plays a major role to maintain the architecture of tissues by fi
 lling the gap between cells\, to provide survival signals and differentiat
 ion signals to cells\, to provide growth factor pools and scaffoldings for
  migration. On the other hand\, ECM is also a physical barrier for migrati
 ng cells in tissues and needs to be degraded in order for cells to migrate
 \nthrough. Because cells require ECM as scaffolding\, degradation of the b
 arrier ECM needs to occur specifically at the direction of the migration. 
  To degrade ECM barrier\, cells utilise proteinases\, and one of the plasm
 a membrane-bound metalloproteinase\, membrane-type 1 matrix metalloprotein
 ase (MT1-MMP) is thought to be a critical enzyme for this process.  MT1-MM
 P is a type I transmembrane proteinase and it degrades various ECM compone
 nts such as collagens type-I\, -II\, -III\, fibronectin\, laminins\, fibri
 n\, aggrecan and so on. It also activates other matrix metalloproteinases 
 (MMPs) namely MMP-2 and MMP13 that have different array of substrate speci
 ficities. Therefore\, expression of MT1-MMP can create multiple enzyme act
 ivities.\n\nMT1-MMP is implicated in many physiological processes and dise
 ases such as wound healing\, bone development\, angiogenesis\, atheroscler
 osis\, cancer progression\, and rheumatoid arthritis. A common feature of 
 these events is a cellular migration/invasion in tissues\, and MT1-MMP is 
 playing a major role.  Such event can be recapiturated by overexpressing t
 he enzyme in the cells which results in enhanced cell motility. MT1-MMP ac
 tivity on the cell surface is precisely regulated not only as a proteinase
  but also as a membrane protein. We have demonstrated that such cellular r
 egulation is essential for MT1-MMP to promote cellular invasion. Disturbin
 g one of the mechanisms supporting its function is enough to inactivate it
 s cell migration promoting activity.\n\nTherefore\, our group is currently
  focusing on critical cellular mechanisms that control MT1-MMP in the hope
  that we would find new means to regulate MT1-MMP function and new treatme
 nt of the diseases such as cancer and rheumatoid arthritis. We employ bioc
 hemical\, molecular biological\, cell biological and structural techniques
  and insights to attack these problems.\n
LOCATION:Lecture Theatre\, Department of Pathology\, Tennis Court Road
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