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Volume 272, Number 52, Issue of December 26, 1997 pp. 32719-32722
(Received for publication, July 25, 1997, and in revised form, October 27, 1997)
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From the Integrin receptors play an important role during
cell migration by mediating linkages and transmitting forces between
the extracellular matrix and the actin cytoskeleton. The mechanisms by
which these linkages are regulated and released during migration are
not well understood. We show here that cell-permeable inhibitors of the
calcium-dependent protease calpain inhibit both 
Department of Cell and Structural Biology,
University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, the
¶ Department of Chemical Engineering and Center for Biomedical
Engineering, Massachusetts Institute of Technology, Cambridge,
Massachusetts 02139, the 
Department of Pharmacology and
Therapeutics, Medical College of Ohio, Toledo, Ohio 43699, and the
** Department of Vascular Biology, The Scripps Research Institute,
La Jolla, California 92037
1 and 3 integrin-mediated cell migration. Calpain inhibition specifically stabilizes peripheral focal adhesions, increases adhesiveness, and
decreases the rate of cell detachment. Furthermore, these inhibitors
alter the fate of integrin receptors at the rear of the cell during
migration. A Chinese hamster ovary cell line expressing low levels of
calpain I also shows reduced migration rates with similar morphological
changes, further implicating calpain in this process. Taken together,
the data suggest that calpain inhibition modulates cell migration by
stabilizing cytoskeletal linkages and decreasing the rate of retraction
of the cell's rear. Inhibiting calpain-mediated proteolysis may
therefore be a potential therapeutic approach to control pathological
cell migration such as tumor metastasis.
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A. Bhatt, I. Kaverina, C. Otey, and A. Huttenlocher Regulation of focal complex composition and disassembly by the calcium-dependent protease calpain J. Cell Sci., January 9, 2002; 115(17): 3415 - 3425. [Abstract] [Full Text] [PDF]
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N. Dourdin, A. K. Bhatt, P. Dutt, P. A. Greer, J. S. C. Arthur, J. S. Elce, and A. Huttenlocher Reduced Cell Migration and Disruption of the Actin Cytoskeleton in Calpain-deficient Embryonic Fibroblasts J. Biol. Chem., December 14, 2001; 276(51): 48382 - 48388. [Abstract] [Full Text] [PDF]
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