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The ability of tumor cells to migrate through the body and invade new tissues is a major focus for research that could leadto new cancer therapies. On page 1345, Uekita et al. demonstrate that the membrane-bound matrix metalloproteinase MT1-MMP, which functions in both migration and invasion, must be recycled continuously from the cell surface to sustain both processes. Blocking the recycling process inhibits the invasive phenotype.
Internalization-defective mutants prevent invasion.
Previous work had shown that MT1-MMP localizes at the migration edge, but it remained unclear how the enzyme was regulated. The authors show that specific sequences in the cytoplasmic tail of MT1-MMP bind to a component of clathrin-coated pits, and that mutations in these sequences prevent internalization and cause the enzyme to accumulate on the cell surface. Although the internalization-defective enzyme specifically accumulates at the migration edge, it does not promote migration or invasion...
The Rockefeller University Press
2001
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