Regulation of Cell Migration by the Calcium-dependent Protease Calpain
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 cel...
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| Veröffentlicht in: | The Journal of biological chemistry 1997-12, Vol.272 (52), p.32719-32722 |
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| container_issue | 52 |
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| container_title | The Journal of biological chemistry |
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| creator | Huttenlocher, Anna Palecek, Sean P. Lu, Qin Zhang, Wenli Mellgren, Ronald L. Lauffenburger, Douglas A. Ginsberg, Mark H. Horwitz, Alan F. |
| description | 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 β1 and β3 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. |
| doi_str_mv | 10.1074/jbc.272.52.32719 |
| format | Article |
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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 β1 and β3 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.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.272.52.32719</identifier><identifier>PMID: 9407041</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Antigens, CD - physiology ; Calpain - antagonists & inhibitors ; Calpain - physiology ; Cell Movement ; CHO Cells ; Cricetinae ; Integrin beta1 - physiology ; Integrin beta3 ; Platelet Membrane Glycoproteins - physiology</subject><ispartof>The Journal of biological chemistry, 1997-12, Vol.272 (52), p.32719-32722</ispartof><rights>1997 © 1997 ASBMB. 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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 β1 and β3 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.</description><subject>Animals</subject><subject>Antigens, CD - physiology</subject><subject>Calpain - antagonists & inhibitors</subject><subject>Calpain - physiology</subject><subject>Cell Movement</subject><subject>CHO Cells</subject><subject>Cricetinae</subject><subject>Integrin beta1 - physiology</subject><subject>Integrin beta3</subject><subject>Platelet Membrane Glycoproteins - physiology</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEtLxDAQx4Mouj7uXoQexFvXJE2b1JsUVwVFEQVvIU2mu5E-1qRV9tsbt4sHQZwcBvJ_MPwQOiZ4SjBn52-lnlJOpymdJpSTfAtNCBZJnKTkdRtNMKYkzmkq9tC-9284DMvJLtrNGeaYkQmaPcF8qFVvuzbqqqiAuo7u7dyNP-Uq6hcQFarWdmhiA0toDbR99Oi6HpRfS0tl20O0U6naw9FmH6CX2dVzcRPfPVzfFpd3sU5J0seCs4yUwoiKZzozvMopNeGxirKUQQUMJ6LU2uQl1okCJtKEZUxo0JSniiQH6GzsXbrufQDfy8Z6HY5WLXSDlzxngpCM_WskGcWUCx6MeDRq13nvoJJLZxvlVpJg-c1YBsYyMJYplWvGIXKy6R7KBsxPYAM16KejvrDzxad1IEvb6QU0v2suRhsEYB8WnPTaQqvBhIjupens3zd8ASTHlfo</recordid><startdate>19971226</startdate><enddate>19971226</enddate><creator>Huttenlocher, Anna</creator><creator>Palecek, Sean P.</creator><creator>Lu, Qin</creator><creator>Zhang, Wenli</creator><creator>Mellgren, Ronald L.</creator><creator>Lauffenburger, Douglas A.</creator><creator>Ginsberg, Mark H.</creator><creator>Horwitz, Alan F.</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7X8</scope></search><sort><creationdate>19971226</creationdate><title>Regulation of Cell Migration by the Calcium-dependent Protease Calpain</title><author>Huttenlocher, Anna ; Palecek, Sean P. ; Lu, Qin ; Zhang, Wenli ; Mellgren, Ronald L. ; Lauffenburger, Douglas A. ; Ginsberg, Mark H. ; Horwitz, Alan F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c513t-87461b8d8f76c6d7f922d2d24f2454efe4038bccd9b0c3ae48534648cec275a13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Animals</topic><topic>Antigens, CD - physiology</topic><topic>Calpain - antagonists & inhibitors</topic><topic>Calpain - physiology</topic><topic>Cell Movement</topic><topic>CHO Cells</topic><topic>Cricetinae</topic><topic>Integrin beta1 - physiology</topic><topic>Integrin beta3</topic><topic>Platelet Membrane Glycoproteins - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Huttenlocher, Anna</creatorcontrib><creatorcontrib>Palecek, Sean P.</creatorcontrib><creatorcontrib>Lu, Qin</creatorcontrib><creatorcontrib>Zhang, Wenli</creatorcontrib><creatorcontrib>Mellgren, Ronald L.</creatorcontrib><creatorcontrib>Lauffenburger, Douglas A.</creatorcontrib><creatorcontrib>Ginsberg, Mark H.</creatorcontrib><creatorcontrib>Horwitz, Alan F.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huttenlocher, Anna</au><au>Palecek, Sean P.</au><au>Lu, Qin</au><au>Zhang, Wenli</au><au>Mellgren, Ronald L.</au><au>Lauffenburger, Douglas A.</au><au>Ginsberg, Mark H.</au><au>Horwitz, Alan F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regulation of Cell Migration by the Calcium-dependent Protease Calpain</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>1997-12-26</date><risdate>1997</risdate><volume>272</volume><issue>52</issue><spage>32719</spage><epage>32722</epage><pages>32719-32722</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>Integrin receptors play an important role during cell migration by mediating linkages and transmitting forces between the extracellular matrix and the actin cytoskeleton. 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Inhibiting calpain-mediated proteolysis may therefore be a potential therapeutic approach to control pathological cell migration such as tumor metastasis.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>9407041</pmid><doi>10.1074/jbc.272.52.32719</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of biological chemistry, 1997-12, Vol.272 (52), p.32719-32722 |
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| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Animals Antigens, CD - physiology Calpain - antagonists & inhibitors Calpain - physiology Cell Movement CHO Cells Cricetinae Integrin beta1 - physiology Integrin beta3 Platelet Membrane Glycoproteins - physiology |
| title | Regulation of Cell Migration by the Calcium-dependent Protease Calpain |
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