Regulation of lamellipodia formation and cell invasion by CLIP-170 in invasive human breast cancer cells
Lamellipodia formation necessary for cell invasion is regulated by Rac1. We report here that lamellipodia formation and three-dimensional invasion were significantly promoted by HGF and serum, respectively, in invasive human breast cancer cells. Rac1 formed a complex with CLIP-170, IQGAP1, and kines...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2008-04, Vol.368 (2), p.199-204 |
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| creator | Suzuki, Katsuo Takahashi, Kazuhide |
| description | Lamellipodia formation necessary for cell invasion is regulated by Rac1. We report here that lamellipodia formation and three-dimensional invasion were significantly promoted by HGF and serum, respectively, in invasive human breast cancer cells. Rac1 formed a complex with CLIP-170, IQGAP1, and kinesin in serum-starved cells, and stimulation of the cells with HGF and serum caused the partial release of IQGAP1 and kinesin from Rac1–CLIP-170 complex. The HGF-induced release of the proteins and promotion of lamellipodia formation were inhibited by an inhibitor of PI3K. Moreover, downregulation of CLIP-170 by siRNA released IQGAP1 and kinesin from Rac1 and promoted lamellipodia formation and invasion, independent of HGF and serum. The results suggest that promotion of lamellipodia formation and invasion by HGF or serum requires PI3K-dependent release of IQGAP1 and kinesin from Rac1–CLIP-170 complex and that CLIP-170 prevents cells from the extracellular stimulus-independent lamellipodia formation and invasion by tethering IQGAP1 and kinesin to Rac1. |
| doi_str_mv | 10.1016/j.bbrc.2008.01.069 |
| format | Article |
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We report here that lamellipodia formation and three-dimensional invasion were significantly promoted by HGF and serum, respectively, in invasive human breast cancer cells. Rac1 formed a complex with CLIP-170, IQGAP1, and kinesin in serum-starved cells, and stimulation of the cells with HGF and serum caused the partial release of IQGAP1 and kinesin from Rac1–CLIP-170 complex. The HGF-induced release of the proteins and promotion of lamellipodia formation were inhibited by an inhibitor of PI3K. Moreover, downregulation of CLIP-170 by siRNA released IQGAP1 and kinesin from Rac1 and promoted lamellipodia formation and invasion, independent of HGF and serum. The results suggest that promotion of lamellipodia formation and invasion by HGF or serum requires PI3K-dependent release of IQGAP1 and kinesin from Rac1–CLIP-170 complex and that CLIP-170 prevents cells from the extracellular stimulus-independent lamellipodia formation and invasion by tethering IQGAP1 and kinesin to Rac1.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2008.01.069</identifier><identifier>PMID: 18237546</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Breast Neoplasms - ultrastructure ; Cell invasion ; Cell Line, Tumor ; CLIP-170 ; Humans ; IQGAP1 ; Kinesin ; Kinesin - metabolism ; Lamellipodia ; Microtubule-Associated Proteins - metabolism ; Neoplasm Invasiveness - pathology ; Neoplasm Invasiveness - ultrastructure ; Neoplasm Proteins - metabolism ; Pseudopodia - metabolism ; Pseudopodia - ultrastructure ; Rac ; rac1 GTP-Binding Protein - metabolism ; ras GTPase-Activating Proteins - metabolism</subject><ispartof>Biochemical and biophysical research communications, 2008-04, Vol.368 (2), p.199-204</ispartof><rights>2008 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c385t-aa605a522cb3d8d6200e6303b251019a758799943f0bfada3654b3f344c019623</citedby><cites>FETCH-LOGICAL-c385t-aa605a522cb3d8d6200e6303b251019a758799943f0bfada3654b3f344c019623</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006291X08000600$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18237546$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Suzuki, Katsuo</creatorcontrib><creatorcontrib>Takahashi, Kazuhide</creatorcontrib><title>Regulation of lamellipodia formation and cell invasion by CLIP-170 in invasive human breast cancer cells</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>Lamellipodia formation necessary for cell invasion is regulated by Rac1. We report here that lamellipodia formation and three-dimensional invasion were significantly promoted by HGF and serum, respectively, in invasive human breast cancer cells. Rac1 formed a complex with CLIP-170, IQGAP1, and kinesin in serum-starved cells, and stimulation of the cells with HGF and serum caused the partial release of IQGAP1 and kinesin from Rac1–CLIP-170 complex. The HGF-induced release of the proteins and promotion of lamellipodia formation were inhibited by an inhibitor of PI3K. Moreover, downregulation of CLIP-170 by siRNA released IQGAP1 and kinesin from Rac1 and promoted lamellipodia formation and invasion, independent of HGF and serum. The results suggest that promotion of lamellipodia formation and invasion by HGF or serum requires PI3K-dependent release of IQGAP1 and kinesin from Rac1–CLIP-170 complex and that CLIP-170 prevents cells from the extracellular stimulus-independent lamellipodia formation and invasion by tethering IQGAP1 and kinesin to Rac1.</description><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Breast Neoplasms - ultrastructure</subject><subject>Cell invasion</subject><subject>Cell Line, Tumor</subject><subject>CLIP-170</subject><subject>Humans</subject><subject>IQGAP1</subject><subject>Kinesin</subject><subject>Kinesin - metabolism</subject><subject>Lamellipodia</subject><subject>Microtubule-Associated Proteins - metabolism</subject><subject>Neoplasm Invasiveness - pathology</subject><subject>Neoplasm Invasiveness - ultrastructure</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Pseudopodia - metabolism</subject><subject>Pseudopodia - ultrastructure</subject><subject>Rac</subject><subject>rac1 GTP-Binding Protein - metabolism</subject><subject>ras GTPase-Activating Proteins - metabolism</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUctKxDAUDaLo-PgBF9KVu9abpE0bcCODLxhQRMFduE1TzdDHmLQD8_emzoA7XQXOi9xzCDmnkFCg4mqZlKXTCQMoEqAJCLlHZhQkxIxCuk9mACBiJun7ETn2fglAaSrkITmiBeN5looZ-XwxH2ODg-27qK-jBlvTNHbVVxajunftlsGuinQgItut0U9IuYnmi8fnmOYQwB2-NtHn2GJgnUE_RBo7bdyP05-Sgxobb8527wl5u7t9nT_Ei6f7x_nNIta8yIYYUUCGGWO65FVRiXCcERx4ybJws8Q8K3IpZcprKGuskIssLXnN01QHWjB-Qi63uSvXf43GD6q1fvoBdqYfvcqBM0EL-a-QQSF4yngQsq1Qu957Z2q1crZFt1EU1DSEWqppCDUNoYCqMEQwXezSx7I11a9l13wQXG8FJpSxtsYpr60JfVXWGT2oqrd_5X8D97GYXg</recordid><startdate>20080404</startdate><enddate>20080404</enddate><creator>Suzuki, Katsuo</creator><creator>Takahashi, Kazuhide</creator><general>Elsevier Inc</general><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>7TM</scope><scope>7X8</scope></search><sort><creationdate>20080404</creationdate><title>Regulation of lamellipodia formation and cell invasion by CLIP-170 in invasive human breast cancer cells</title><author>Suzuki, Katsuo ; Takahashi, Kazuhide</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c385t-aa605a522cb3d8d6200e6303b251019a758799943f0bfada3654b3f344c019623</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - pathology</topic><topic>Breast Neoplasms - ultrastructure</topic><topic>Cell invasion</topic><topic>Cell Line, Tumor</topic><topic>CLIP-170</topic><topic>Humans</topic><topic>IQGAP1</topic><topic>Kinesin</topic><topic>Kinesin - metabolism</topic><topic>Lamellipodia</topic><topic>Microtubule-Associated Proteins - metabolism</topic><topic>Neoplasm Invasiveness - pathology</topic><topic>Neoplasm Invasiveness - ultrastructure</topic><topic>Neoplasm Proteins - metabolism</topic><topic>Pseudopodia - metabolism</topic><topic>Pseudopodia - ultrastructure</topic><topic>Rac</topic><topic>rac1 GTP-Binding Protein - metabolism</topic><topic>ras GTPase-Activating Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Suzuki, Katsuo</creatorcontrib><creatorcontrib>Takahashi, Kazuhide</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Suzuki, Katsuo</au><au>Takahashi, Kazuhide</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regulation of lamellipodia formation and cell invasion by CLIP-170 in invasive human breast cancer cells</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2008-04-04</date><risdate>2008</risdate><volume>368</volume><issue>2</issue><spage>199</spage><epage>204</epage><pages>199-204</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Lamellipodia formation necessary for cell invasion is regulated by Rac1. We report here that lamellipodia formation and three-dimensional invasion were significantly promoted by HGF and serum, respectively, in invasive human breast cancer cells. Rac1 formed a complex with CLIP-170, IQGAP1, and kinesin in serum-starved cells, and stimulation of the cells with HGF and serum caused the partial release of IQGAP1 and kinesin from Rac1–CLIP-170 complex. The HGF-induced release of the proteins and promotion of lamellipodia formation were inhibited by an inhibitor of PI3K. Moreover, downregulation of CLIP-170 by siRNA released IQGAP1 and kinesin from Rac1 and promoted lamellipodia formation and invasion, independent of HGF and serum. The results suggest that promotion of lamellipodia formation and invasion by HGF or serum requires PI3K-dependent release of IQGAP1 and kinesin from Rac1–CLIP-170 complex and that CLIP-170 prevents cells from the extracellular stimulus-independent lamellipodia formation and invasion by tethering IQGAP1 and kinesin to Rac1.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>18237546</pmid><doi>10.1016/j.bbrc.2008.01.069</doi><tpages>6</tpages></addata></record> |
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| subjects | Breast Neoplasms - metabolism Breast Neoplasms - pathology Breast Neoplasms - ultrastructure Cell invasion Cell Line, Tumor CLIP-170 Humans IQGAP1 Kinesin Kinesin - metabolism Lamellipodia Microtubule-Associated Proteins - metabolism Neoplasm Invasiveness - pathology Neoplasm Invasiveness - ultrastructure Neoplasm Proteins - metabolism Pseudopodia - metabolism Pseudopodia - ultrastructure Rac rac1 GTP-Binding Protein - metabolism ras GTPase-Activating Proteins - metabolism |
| title | Regulation of lamellipodia formation and cell invasion by CLIP-170 in invasive human breast cancer cells |
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