Receptor tyrosine kinase Met promotes cell survival via kinase-independent maintenance of integrin α3β1
Matrix adhesion via integrins is required for cell survival. Adhesion of epithelial cells to laminin via integrin α3β1 was previously shown to activate at least two independent survival pathways. First, integrin α3β1 is required for autophagy-induced cell survival after growth factor deprivation. Se...
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Veröffentlicht in: | Molecular biology of the cell 2016-08, Vol.27 (15), p.2493-2504 |
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creator | Tesfay, Lia Schulz, Veronique V Frank, Sander B Lamb, Laura E Miranti, Cindy K |
description | Matrix adhesion via integrins is required for cell survival. Adhesion of epithelial cells to laminin via integrin α3β1 was previously shown to activate at least two independent survival pathways. First, integrin α3β1 is required for autophagy-induced cell survival after growth factor deprivation. Second, integrin α3β1 independently activates two receptor tyrosine kinases, EGFR and Met, in the absence of ligands. EGFR signaling to Erk promotes survival independently of autophagy. To determine how Met promotes cell survival, we inhibited Met kinase activity or blocked its expression with RNA interference. Loss of Met expression, but not inhibition of Met kinase activity, induced apoptosis by reducing integrin α3β1 levels, activating anoikis, and blocking autophagy. Met was specifically required for the assembly of autophagosomes downstream of LC3II processing. Reexpression of wild-type Met, kinase-dead Met, or integrin α3 was sufficient to rescue death upon removal of endogenous Met. Integrin α3β1 coprecipitated and colocalized with Met in cells. The extracellular and transmembrane domain of Met was required to fully rescue cell death and restore integrin α3 expression. Thus Met promotes survival of laminin-adherent cells by maintaining integrin α3β1 via a kinase-independent mechanism. |
doi_str_mv | 10.1091/mbc.E15-09-0649 |
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Silvio</contributor><creatorcontrib>Tesfay, Lia ; Schulz, Veronique V ; Frank, Sander B ; Lamb, Laura E ; Miranti, Cindy K ; Gutkind, J. Silvio</creatorcontrib><description>Matrix adhesion via integrins is required for cell survival. Adhesion of epithelial cells to laminin via integrin α3β1 was previously shown to activate at least two independent survival pathways. First, integrin α3β1 is required for autophagy-induced cell survival after growth factor deprivation. Second, integrin α3β1 independently activates two receptor tyrosine kinases, EGFR and Met, in the absence of ligands. EGFR signaling to Erk promotes survival independently of autophagy. To determine how Met promotes cell survival, we inhibited Met kinase activity or blocked its expression with RNA interference. Loss of Met expression, but not inhibition of Met kinase activity, induced apoptosis by reducing integrin α3β1 levels, activating anoikis, and blocking autophagy. Met was specifically required for the assembly of autophagosomes downstream of LC3II processing. Reexpression of wild-type Met, kinase-dead Met, or integrin α3 was sufficient to rescue death upon removal of endogenous Met. Integrin α3β1 coprecipitated and colocalized with Met in cells. The extracellular and transmembrane domain of Met was required to fully rescue cell death and restore integrin α3 expression. Thus Met promotes survival of laminin-adherent cells by maintaining integrin α3β1 via a kinase-independent mechanism.</description><identifier>ISSN: 1059-1524</identifier><identifier>EISSN: 1939-4586</identifier><identifier>DOI: 10.1091/mbc.E15-09-0649</identifier><identifier>PMID: 27307589</identifier><language>eng</language><publisher>United States: The American Society for Cell Biology</publisher><subject>Apoptosis ; Cell Adhesion - physiology ; Cell Death ; Cell Survival - physiology ; Epithelial Cells - metabolism ; Extracellular Matrix - metabolism ; Humans ; Integrin alpha3beta1 - genetics ; Integrin alpha3beta1 - metabolism ; Integrins - metabolism ; Laminin - metabolism ; Male ; MAP Kinase Signaling System ; Matrix Attachment Regions ; Phosphorylation ; Primary Cell Culture ; Prostate ; Proto-Oncogene Proteins c-met - metabolism ; Receptor Protein-Tyrosine Kinases - metabolism ; Signal Transduction</subject><ispartof>Molecular biology of the cell, 2016-08, Vol.27 (15), p.2493-2504</ispartof><rights>2016 Tesfay, Schulz, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).</rights><rights>2016 Tesfay, Schulz, This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License ( ). 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4209-538d48da222de8ede702708d0cf29c536f328bc3b1a5a417e1605def18fb98593</citedby><cites>FETCH-LOGICAL-c4209-538d48da222de8ede702708d0cf29c536f328bc3b1a5a417e1605def18fb98593</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966988/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966988/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27307589$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Gutkind, J. Silvio</contributor><creatorcontrib>Tesfay, Lia</creatorcontrib><creatorcontrib>Schulz, Veronique V</creatorcontrib><creatorcontrib>Frank, Sander B</creatorcontrib><creatorcontrib>Lamb, Laura E</creatorcontrib><creatorcontrib>Miranti, Cindy K</creatorcontrib><title>Receptor tyrosine kinase Met promotes cell survival via kinase-independent maintenance of integrin α3β1</title><title>Molecular biology of the cell</title><addtitle>Mol Biol Cell</addtitle><description>Matrix adhesion via integrins is required for cell survival. Adhesion of epithelial cells to laminin via integrin α3β1 was previously shown to activate at least two independent survival pathways. First, integrin α3β1 is required for autophagy-induced cell survival after growth factor deprivation. Second, integrin α3β1 independently activates two receptor tyrosine kinases, EGFR and Met, in the absence of ligands. EGFR signaling to Erk promotes survival independently of autophagy. To determine how Met promotes cell survival, we inhibited Met kinase activity or blocked its expression with RNA interference. Loss of Met expression, but not inhibition of Met kinase activity, induced apoptosis by reducing integrin α3β1 levels, activating anoikis, and blocking autophagy. Met was specifically required for the assembly of autophagosomes downstream of LC3II processing. Reexpression of wild-type Met, kinase-dead Met, or integrin α3 was sufficient to rescue death upon removal of endogenous Met. Integrin α3β1 coprecipitated and colocalized with Met in cells. The extracellular and transmembrane domain of Met was required to fully rescue cell death and restore integrin α3 expression. Thus Met promotes survival of laminin-adherent cells by maintaining integrin α3β1 via a kinase-independent mechanism.</description><subject>Apoptosis</subject><subject>Cell Adhesion - physiology</subject><subject>Cell Death</subject><subject>Cell Survival - physiology</subject><subject>Epithelial Cells - metabolism</subject><subject>Extracellular Matrix - metabolism</subject><subject>Humans</subject><subject>Integrin alpha3beta1 - genetics</subject><subject>Integrin alpha3beta1 - metabolism</subject><subject>Integrins - metabolism</subject><subject>Laminin - metabolism</subject><subject>Male</subject><subject>MAP Kinase Signaling System</subject><subject>Matrix Attachment Regions</subject><subject>Phosphorylation</subject><subject>Primary Cell Culture</subject><subject>Prostate</subject><subject>Proto-Oncogene Proteins c-met - metabolism</subject><subject>Receptor Protein-Tyrosine Kinases - metabolism</subject><subject>Signal Transduction</subject><issn>1059-1524</issn><issn>1939-4586</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUctO3DAUtVARMzzW3VVedhPGz8TeVKoQbZGokBCsLce5AbeJndqZkfgs-JD5pnrEFJXNfeiee-7jIPSRknNKNF2NrTu_pLIiuiK10AdoSTXXlZCq_lBiInVFJRMLdJzzL0KoEHVzhBas4aSRSi-RvwUH0xwTnp9SzD4A_u2DzYB_woynFMc4Q8YOhgHnddr4jR3wxts9qvKhgwmKCTMerQ8zBBsc4NjjXfKQfMDbZ759oafosLdDhrO9P0H33y7vLn5U1zffry6-XldOsHKG5KoTqrOMsQ4UdNAQ1hDVEdcz7SSve85U63hLrbSCNkBrIjvoqepbraTmJ-jLK--0bkfoXNks2cFMyY82PZlovXlfCf7RPMSNEbqutVKF4POeIMU_a8izGX3ePcAGiOtsqCKNUkJrWqCrV6grv8sJ-rcxlJidQKYIZIBKQ7TZCVQ6Pv2_3Rv-nyL8L-kkkOA</recordid><startdate>20160801</startdate><enddate>20160801</enddate><creator>Tesfay, Lia</creator><creator>Schulz, Veronique V</creator><creator>Frank, Sander B</creator><creator>Lamb, Laura E</creator><creator>Miranti, Cindy K</creator><general>The American Society for Cell Biology</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160801</creationdate><title>Receptor tyrosine kinase Met promotes cell survival via kinase-independent maintenance of integrin α3β1</title><author>Tesfay, Lia ; Schulz, Veronique V ; Frank, Sander B ; Lamb, Laura E ; Miranti, Cindy K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4209-538d48da222de8ede702708d0cf29c536f328bc3b1a5a417e1605def18fb98593</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Apoptosis</topic><topic>Cell Adhesion - physiology</topic><topic>Cell Death</topic><topic>Cell Survival - physiology</topic><topic>Epithelial Cells - metabolism</topic><topic>Extracellular Matrix - metabolism</topic><topic>Humans</topic><topic>Integrin alpha3beta1 - genetics</topic><topic>Integrin alpha3beta1 - metabolism</topic><topic>Integrins - metabolism</topic><topic>Laminin - metabolism</topic><topic>Male</topic><topic>MAP Kinase Signaling System</topic><topic>Matrix Attachment Regions</topic><topic>Phosphorylation</topic><topic>Primary Cell Culture</topic><topic>Prostate</topic><topic>Proto-Oncogene Proteins c-met - metabolism</topic><topic>Receptor Protein-Tyrosine Kinases - metabolism</topic><topic>Signal Transduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tesfay, Lia</creatorcontrib><creatorcontrib>Schulz, Veronique V</creatorcontrib><creatorcontrib>Frank, Sander B</creatorcontrib><creatorcontrib>Lamb, Laura E</creatorcontrib><creatorcontrib>Miranti, Cindy K</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular biology of the cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tesfay, Lia</au><au>Schulz, Veronique V</au><au>Frank, Sander B</au><au>Lamb, Laura E</au><au>Miranti, Cindy K</au><au>Gutkind, J. Silvio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Receptor tyrosine kinase Met promotes cell survival via kinase-independent maintenance of integrin α3β1</atitle><jtitle>Molecular biology of the cell</jtitle><addtitle>Mol Biol Cell</addtitle><date>2016-08-01</date><risdate>2016</risdate><volume>27</volume><issue>15</issue><spage>2493</spage><epage>2504</epage><pages>2493-2504</pages><issn>1059-1524</issn><eissn>1939-4586</eissn><abstract>Matrix adhesion via integrins is required for cell survival. Adhesion of epithelial cells to laminin via integrin α3β1 was previously shown to activate at least two independent survival pathways. First, integrin α3β1 is required for autophagy-induced cell survival after growth factor deprivation. Second, integrin α3β1 independently activates two receptor tyrosine kinases, EGFR and Met, in the absence of ligands. EGFR signaling to Erk promotes survival independently of autophagy. To determine how Met promotes cell survival, we inhibited Met kinase activity or blocked its expression with RNA interference. Loss of Met expression, but not inhibition of Met kinase activity, induced apoptosis by reducing integrin α3β1 levels, activating anoikis, and blocking autophagy. Met was specifically required for the assembly of autophagosomes downstream of LC3II processing. Reexpression of wild-type Met, kinase-dead Met, or integrin α3 was sufficient to rescue death upon removal of endogenous Met. Integrin α3β1 coprecipitated and colocalized with Met in cells. The extracellular and transmembrane domain of Met was required to fully rescue cell death and restore integrin α3 expression. 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subjects | Apoptosis Cell Adhesion - physiology Cell Death Cell Survival - physiology Epithelial Cells - metabolism Extracellular Matrix - metabolism Humans Integrin alpha3beta1 - genetics Integrin alpha3beta1 - metabolism Integrins - metabolism Laminin - metabolism Male MAP Kinase Signaling System Matrix Attachment Regions Phosphorylation Primary Cell Culture Prostate Proto-Oncogene Proteins c-met - metabolism Receptor Protein-Tyrosine Kinases - metabolism Signal Transduction |
title | Receptor tyrosine kinase Met promotes cell survival via kinase-independent maintenance of integrin α3β1 |
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