Src kinase activity coordinates cell adhesion and spreading with activation of mammalian target of rapamycin in pancreatic endocrine tumour cells
Pancreatic endocrine tumours (PETs) are rare and heterogeneous neoplasms, often diagnosed at metastatic stage, for which no cure is currently available. Recently, activation of two pathways that support proliferation and invasiveness of cancer cells, the Src family kinase (SFK) and mammalian target...
Gespeichert in:
Veröffentlicht in: | Endocrine-related cancer 2011-10, Vol.18 (5), p.541-554 |
---|---|
Hauptverfasser: | , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 554 |
---|---|
container_issue | 5 |
container_start_page | 541 |
container_title | Endocrine-related cancer |
container_volume | 18 |
creator | Di Florio, Alessia Adesso, Laura Pedrotti, Simona Capurso, Gabriele Pilozzi, Emanuela Corbo, Vincenzo Scarpa, Aldo Geremia, Raffaele Delle Fave, Gianfranco Sette, Claudio |
description | Pancreatic endocrine tumours (PETs) are rare and heterogeneous neoplasms, often diagnosed at metastatic stage, for which no cure is currently available. Recently, activation of two pathways that support proliferation and invasiveness of cancer cells, the Src family kinase (SFK) and mammalian target of rapamycin (mTOR) pathways, was demonstrated in PETs. Since both pathways represent suitable targets for therapeutic intervention, we investigated their possible interaction in PETs. Western blot and immunofluorescence analyses indicated that SFK and mTOR activity correlate in PET cell lines. We also found that SFKs coordinate cell adhesion and spreading with activation of the mTOR pathway in PET cells. Live cell metabolic labelling and biochemical studies demonstrated that SFK activity enhance mTOR-dependent translation initiation. Furthermore, microarray analysis of the mRNAs associated with polyribosomes revealed that SFKs regulate mTOR-dependent translation of specific transcripts, with an enrichment in mRNAs encoding cell cycle proteins. Importantly, a synergic inhibition of proliferation was observed in PET cells concomitantly treated with SFK and mTOR inhibitors, without activation of the phosphatidylinositol 3-kinase/AKT pro-survival pathway. Tissue microarray analysis revealed activation of Src and mTOR in some PET samples, and identified phosphorylation of 4E-BP1 as an independent marker of poor prognosis in PETs. Thus, our work highlights a novel link between the SFK and mTOR pathways, which regulate the translation of mRNAs for cell cycle regulators, and suggest that crosstalk between these pathways promotes PET cell proliferation. |
doi_str_mv | 10.1530/ERC-10-0153 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_886917040</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>886917040</sourcerecordid><originalsourceid>FETCH-LOGICAL-b410t-40ac76233c8d6da39d288ad7497d59e54d36b682098cd3f1f237e2f7ebe3fd9a3</originalsourceid><addsrcrecordid>eNp9kcuKFTEQhoMozkVX7iU7F9KadPqSXsphdIQBwcu6qU6qzyk9nbRJ2uE8hm9s2p4RcSEEUqn6_kpRP2PPpHglayVeX33cFVIUIj8esHNZtV3R6FI-zLGqZSGE1mfsIsavQohG1_VjdlbKVpaqas7Zz0_B8G_kICIHk-gHpRM33gebcwkjN3g8crAHjOQdB2d5nANCLu_5LaXDpoK0Vv3IJ5gmOBI4niDsMa25ADNMJ0OO5zODM1mfyHB01ptADnlaJr-E33_FJ-zRCMeIT-_uS_bl7dXn3XVx8-Hd-92bm2KopEhFJcC0TamU0baxoDpbag22rbrW1h3WlVXNkPcgOm2sGuVYqhbLscUB1Wg7UJfsxdZ3Dv77gjH1E8V1AnDol9hr3XSyFZXI5MuNNMHHGHDs50AThFMvRb9a0GcL1ni1INPP7_ouw4T2D3u_8wyUG3Cg_eGWAvYD-WgIXaKRDPzd9d7YLJKb6B_2f5P8AgZipQI</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>886917040</pqid></control><display><type>article</type><title>Src kinase activity coordinates cell adhesion and spreading with activation of mammalian target of rapamycin in pancreatic endocrine tumour cells</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><source>Society for Endocrinology Journals</source><creator>Di Florio, Alessia ; Adesso, Laura ; Pedrotti, Simona ; Capurso, Gabriele ; Pilozzi, Emanuela ; Corbo, Vincenzo ; Scarpa, Aldo ; Geremia, Raffaele ; Delle Fave, Gianfranco ; Sette, Claudio</creator><creatorcontrib>Di Florio, Alessia ; Adesso, Laura ; Pedrotti, Simona ; Capurso, Gabriele ; Pilozzi, Emanuela ; Corbo, Vincenzo ; Scarpa, Aldo ; Geremia, Raffaele ; Delle Fave, Gianfranco ; Sette, Claudio</creatorcontrib><description>Pancreatic endocrine tumours (PETs) are rare and heterogeneous neoplasms, often diagnosed at metastatic stage, for which no cure is currently available. Recently, activation of two pathways that support proliferation and invasiveness of cancer cells, the Src family kinase (SFK) and mammalian target of rapamycin (mTOR) pathways, was demonstrated in PETs. Since both pathways represent suitable targets for therapeutic intervention, we investigated their possible interaction in PETs. Western blot and immunofluorescence analyses indicated that SFK and mTOR activity correlate in PET cell lines. We also found that SFKs coordinate cell adhesion and spreading with activation of the mTOR pathway in PET cells. Live cell metabolic labelling and biochemical studies demonstrated that SFK activity enhance mTOR-dependent translation initiation. Furthermore, microarray analysis of the mRNAs associated with polyribosomes revealed that SFKs regulate mTOR-dependent translation of specific transcripts, with an enrichment in mRNAs encoding cell cycle proteins. Importantly, a synergic inhibition of proliferation was observed in PET cells concomitantly treated with SFK and mTOR inhibitors, without activation of the phosphatidylinositol 3-kinase/AKT pro-survival pathway. Tissue microarray analysis revealed activation of Src and mTOR in some PET samples, and identified phosphorylation of 4E-BP1 as an independent marker of poor prognosis in PETs. Thus, our work highlights a novel link between the SFK and mTOR pathways, which regulate the translation of mRNAs for cell cycle regulators, and suggest that crosstalk between these pathways promotes PET cell proliferation.</description><identifier>ISSN: 1351-0088</identifier><identifier>EISSN: 1479-6821</identifier><identifier>DOI: 10.1530/ERC-10-0153</identifier><identifier>PMID: 21712346</identifier><language>eng</language><publisher>England: Society for Endocrinology</publisher><subject>Cell Adhesion - physiology ; Cell Cycle Proteins - genetics ; Cell Cycle Proteins - metabolism ; Cell Line, Tumor ; Humans ; Neuroendocrine Tumors - enzymology ; Neuroendocrine Tumors - metabolism ; Neuroendocrine Tumors - pathology ; Pancreatic Neoplasms - enzymology ; Pancreatic Neoplasms - metabolism ; Pancreatic Neoplasms - pathology ; Regular papers ; RNA, Messenger - chemistry ; RNA, Messenger - genetics ; src-Family Kinases - metabolism ; Tissue Array Analysis ; TOR Serine-Threonine Kinases - metabolism</subject><ispartof>Endocrine-related cancer, 2011-10, Vol.18 (5), p.541-554</ispartof><rights>2011 Society for Endocrinology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b410t-40ac76233c8d6da39d288ad7497d59e54d36b682098cd3f1f237e2f7ebe3fd9a3</citedby><cites>FETCH-LOGICAL-b410t-40ac76233c8d6da39d288ad7497d59e54d36b682098cd3f1f237e2f7ebe3fd9a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3936,3937,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21712346$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Di Florio, Alessia</creatorcontrib><creatorcontrib>Adesso, Laura</creatorcontrib><creatorcontrib>Pedrotti, Simona</creatorcontrib><creatorcontrib>Capurso, Gabriele</creatorcontrib><creatorcontrib>Pilozzi, Emanuela</creatorcontrib><creatorcontrib>Corbo, Vincenzo</creatorcontrib><creatorcontrib>Scarpa, Aldo</creatorcontrib><creatorcontrib>Geremia, Raffaele</creatorcontrib><creatorcontrib>Delle Fave, Gianfranco</creatorcontrib><creatorcontrib>Sette, Claudio</creatorcontrib><title>Src kinase activity coordinates cell adhesion and spreading with activation of mammalian target of rapamycin in pancreatic endocrine tumour cells</title><title>Endocrine-related cancer</title><addtitle>Endocr Relat Cancer</addtitle><description>Pancreatic endocrine tumours (PETs) are rare and heterogeneous neoplasms, often diagnosed at metastatic stage, for which no cure is currently available. Recently, activation of two pathways that support proliferation and invasiveness of cancer cells, the Src family kinase (SFK) and mammalian target of rapamycin (mTOR) pathways, was demonstrated in PETs. Since both pathways represent suitable targets for therapeutic intervention, we investigated their possible interaction in PETs. Western blot and immunofluorescence analyses indicated that SFK and mTOR activity correlate in PET cell lines. We also found that SFKs coordinate cell adhesion and spreading with activation of the mTOR pathway in PET cells. Live cell metabolic labelling and biochemical studies demonstrated that SFK activity enhance mTOR-dependent translation initiation. Furthermore, microarray analysis of the mRNAs associated with polyribosomes revealed that SFKs regulate mTOR-dependent translation of specific transcripts, with an enrichment in mRNAs encoding cell cycle proteins. Importantly, a synergic inhibition of proliferation was observed in PET cells concomitantly treated with SFK and mTOR inhibitors, without activation of the phosphatidylinositol 3-kinase/AKT pro-survival pathway. Tissue microarray analysis revealed activation of Src and mTOR in some PET samples, and identified phosphorylation of 4E-BP1 as an independent marker of poor prognosis in PETs. Thus, our work highlights a novel link between the SFK and mTOR pathways, which regulate the translation of mRNAs for cell cycle regulators, and suggest that crosstalk between these pathways promotes PET cell proliferation.</description><subject>Cell Adhesion - physiology</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Humans</subject><subject>Neuroendocrine Tumors - enzymology</subject><subject>Neuroendocrine Tumors - metabolism</subject><subject>Neuroendocrine Tumors - pathology</subject><subject>Pancreatic Neoplasms - enzymology</subject><subject>Pancreatic Neoplasms - metabolism</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Regular papers</subject><subject>RNA, Messenger - chemistry</subject><subject>RNA, Messenger - genetics</subject><subject>src-Family Kinases - metabolism</subject><subject>Tissue Array Analysis</subject><subject>TOR Serine-Threonine Kinases - metabolism</subject><issn>1351-0088</issn><issn>1479-6821</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcuKFTEQhoMozkVX7iU7F9KadPqSXsphdIQBwcu6qU6qzyk9nbRJ2uE8hm9s2p4RcSEEUqn6_kpRP2PPpHglayVeX33cFVIUIj8esHNZtV3R6FI-zLGqZSGE1mfsIsavQohG1_VjdlbKVpaqas7Zz0_B8G_kICIHk-gHpRM33gebcwkjN3g8crAHjOQdB2d5nANCLu_5LaXDpoK0Vv3IJ5gmOBI4niDsMa25ADNMJ0OO5zODM1mfyHB01ptADnlaJr-E33_FJ-zRCMeIT-_uS_bl7dXn3XVx8-Hd-92bm2KopEhFJcC0TamU0baxoDpbag22rbrW1h3WlVXNkPcgOm2sGuVYqhbLscUB1Wg7UJfsxdZ3Dv77gjH1E8V1AnDol9hr3XSyFZXI5MuNNMHHGHDs50AThFMvRb9a0GcL1ni1INPP7_ouw4T2D3u_8wyUG3Cg_eGWAvYD-WgIXaKRDPzd9d7YLJKb6B_2f5P8AgZipQI</recordid><startdate>201110</startdate><enddate>201110</enddate><creator>Di Florio, Alessia</creator><creator>Adesso, Laura</creator><creator>Pedrotti, Simona</creator><creator>Capurso, Gabriele</creator><creator>Pilozzi, Emanuela</creator><creator>Corbo, Vincenzo</creator><creator>Scarpa, Aldo</creator><creator>Geremia, Raffaele</creator><creator>Delle Fave, Gianfranco</creator><creator>Sette, Claudio</creator><general>Society for Endocrinology</general><general>BioScientifica</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></search><sort><creationdate>201110</creationdate><title>Src kinase activity coordinates cell adhesion and spreading with activation of mammalian target of rapamycin in pancreatic endocrine tumour cells</title><author>Di Florio, Alessia ; Adesso, Laura ; Pedrotti, Simona ; Capurso, Gabriele ; Pilozzi, Emanuela ; Corbo, Vincenzo ; Scarpa, Aldo ; Geremia, Raffaele ; Delle Fave, Gianfranco ; Sette, Claudio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b410t-40ac76233c8d6da39d288ad7497d59e54d36b682098cd3f1f237e2f7ebe3fd9a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Cell Adhesion - physiology</topic><topic>Cell Cycle Proteins - genetics</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Humans</topic><topic>Neuroendocrine Tumors - enzymology</topic><topic>Neuroendocrine Tumors - metabolism</topic><topic>Neuroendocrine Tumors - pathology</topic><topic>Pancreatic Neoplasms - enzymology</topic><topic>Pancreatic Neoplasms - metabolism</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Regular papers</topic><topic>RNA, Messenger - chemistry</topic><topic>RNA, Messenger - genetics</topic><topic>src-Family Kinases - metabolism</topic><topic>Tissue Array Analysis</topic><topic>TOR Serine-Threonine Kinases - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Di Florio, Alessia</creatorcontrib><creatorcontrib>Adesso, Laura</creatorcontrib><creatorcontrib>Pedrotti, Simona</creatorcontrib><creatorcontrib>Capurso, Gabriele</creatorcontrib><creatorcontrib>Pilozzi, Emanuela</creatorcontrib><creatorcontrib>Corbo, Vincenzo</creatorcontrib><creatorcontrib>Scarpa, Aldo</creatorcontrib><creatorcontrib>Geremia, Raffaele</creatorcontrib><creatorcontrib>Delle Fave, Gianfranco</creatorcontrib><creatorcontrib>Sette, Claudio</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><jtitle>Endocrine-related cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Di Florio, Alessia</au><au>Adesso, Laura</au><au>Pedrotti, Simona</au><au>Capurso, Gabriele</au><au>Pilozzi, Emanuela</au><au>Corbo, Vincenzo</au><au>Scarpa, Aldo</au><au>Geremia, Raffaele</au><au>Delle Fave, Gianfranco</au><au>Sette, Claudio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Src kinase activity coordinates cell adhesion and spreading with activation of mammalian target of rapamycin in pancreatic endocrine tumour cells</atitle><jtitle>Endocrine-related cancer</jtitle><addtitle>Endocr Relat Cancer</addtitle><date>2011-10</date><risdate>2011</risdate><volume>18</volume><issue>5</issue><spage>541</spage><epage>554</epage><pages>541-554</pages><issn>1351-0088</issn><eissn>1479-6821</eissn><abstract>Pancreatic endocrine tumours (PETs) are rare and heterogeneous neoplasms, often diagnosed at metastatic stage, for which no cure is currently available. Recently, activation of two pathways that support proliferation and invasiveness of cancer cells, the Src family kinase (SFK) and mammalian target of rapamycin (mTOR) pathways, was demonstrated in PETs. Since both pathways represent suitable targets for therapeutic intervention, we investigated their possible interaction in PETs. Western blot and immunofluorescence analyses indicated that SFK and mTOR activity correlate in PET cell lines. We also found that SFKs coordinate cell adhesion and spreading with activation of the mTOR pathway in PET cells. Live cell metabolic labelling and biochemical studies demonstrated that SFK activity enhance mTOR-dependent translation initiation. Furthermore, microarray analysis of the mRNAs associated with polyribosomes revealed that SFKs regulate mTOR-dependent translation of specific transcripts, with an enrichment in mRNAs encoding cell cycle proteins. Importantly, a synergic inhibition of proliferation was observed in PET cells concomitantly treated with SFK and mTOR inhibitors, without activation of the phosphatidylinositol 3-kinase/AKT pro-survival pathway. Tissue microarray analysis revealed activation of Src and mTOR in some PET samples, and identified phosphorylation of 4E-BP1 as an independent marker of poor prognosis in PETs. Thus, our work highlights a novel link between the SFK and mTOR pathways, which regulate the translation of mRNAs for cell cycle regulators, and suggest that crosstalk between these pathways promotes PET cell proliferation.</abstract><cop>England</cop><pub>Society for Endocrinology</pub><pmid>21712346</pmid><doi>10.1530/ERC-10-0153</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1351-0088 |
ispartof | Endocrine-related cancer, 2011-10, Vol.18 (5), p.541-554 |
issn | 1351-0088 1479-6821 |
language | eng |
recordid | cdi_proquest_miscellaneous_886917040 |
source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection; Society for Endocrinology Journals |
subjects | Cell Adhesion - physiology Cell Cycle Proteins - genetics Cell Cycle Proteins - metabolism Cell Line, Tumor Humans Neuroendocrine Tumors - enzymology Neuroendocrine Tumors - metabolism Neuroendocrine Tumors - pathology Pancreatic Neoplasms - enzymology Pancreatic Neoplasms - metabolism Pancreatic Neoplasms - pathology Regular papers RNA, Messenger - chemistry RNA, Messenger - genetics src-Family Kinases - metabolism Tissue Array Analysis TOR Serine-Threonine Kinases - metabolism |
title | Src kinase activity coordinates cell adhesion and spreading with activation of mammalian target of rapamycin in pancreatic endocrine tumour cells |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T19%3A54%3A07IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Src%20kinase%20activity%20coordinates%20cell%20adhesion%20and%20spreading%20with%20activation%20of%20mammalian%20target%20of%20rapamycin%20in%20pancreatic%20endocrine%20tumour%20cells&rft.jtitle=Endocrine-related%20cancer&rft.au=Di%20Florio,%20Alessia&rft.date=2011-10&rft.volume=18&rft.issue=5&rft.spage=541&rft.epage=554&rft.pages=541-554&rft.issn=1351-0088&rft.eissn=1479-6821&rft_id=info:doi/10.1530/ERC-10-0153&rft_dat=%3Cproquest_cross%3E886917040%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=886917040&rft_id=info:pmid/21712346&rfr_iscdi=true |