tumor suppressor activity of IKKα in stratified epithelia is exerted in part via the TGF-β antiproliferative pathway
The transforming growth factor type β-1 (TGF-β) signaling pathway is a major tumor suppressor during early carcinogenesis, and its growth-suppressive activity is commonly lost during early tumor progression. IκB kinase α (IKKα) also acts as a tumor suppressor in stratified epithelia, and its express...
Gespeichert in:
| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2008-11, Vol.105 (44), p.17091-17096 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 17096 |
|---|---|
| container_issue | 44 |
| container_start_page | 17091 |
| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 105 |
| creator | Marinari, Barbara Moretti, Francesca Botti, Elisabetta Giustizieri, Maria Laura Descargues, Pascal Giunta, Alessandro Stolfi, Carmine Ballaro, Costanza Papoutsaki, Marina Alemà, Stefano Monteleone, Giovanni Chimenti, Sergio Karin, Michael Costanzo, Antonio |
| description | The transforming growth factor type β-1 (TGF-β) signaling pathway is a major tumor suppressor during early carcinogenesis, and its growth-suppressive activity is commonly lost during early tumor progression. IκB kinase α (IKKα) also acts as a tumor suppressor in stratified epithelia, and its expression and nuclear localization are progressively down-regulated during malignant progression of squamous cell carcinoma (SCC) and acquisition of an invasive phenotype. A critical role for IKKα in TGF-β signaling in stratified epithelia was identified recently during normal keratinocyte differentiation, and both IKKα and components of the TGF-β signaling pathway are required for induction of antiproliferative Myc antagonists in such cells. We now describe that the interaction between IKKα and the TGF-β signaling pathway is also important in a subset of SCCs. In SCCs that are unable to shuttle IKKα to the nucleus, defective TGF-β-induced growth arrest was rescued by introduction of a constitutively nuclear IKKα variant. These results suggest that the tumor-suppressive activity of IKKα in stratified epithelia may be exerted in part via the TGF-β signaling pathway. |
| doi_str_mv | 10.1073/pnas.0809288105 |
| format | Article |
| fullrecord | <record><control><sourceid>jstor_pnas_</sourceid><recordid>TN_cdi_pnas_primary_105_44_17091</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><jstor_id>25465230</jstor_id><sourcerecordid>25465230</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3885-49b0026ee7f9e34cc4fa348351356e124773d6012643584693e58fc36a801a5a3</originalsourceid><addsrcrecordid>eNqFkb9uFDEQxi0EIkegpkK4QqLYxH_XdoMURSREiURBUlvO3jjnaG-92N4l91jwIHkmfLpTIiqqGc33m88efQi9p-SIEsWPx8HlI6KJYVpTIl-gBSWGNq0w5CVaEMJUowUTB-hNzveEECM1eY0OqDZSSUkXaC7TOiacp3FMkHNtXVfCHMoGR48vLi8ff-Mw4FySK8EHWGIYQ1lBHxwOGcMDpFKHFRldKniu46ri6_Oz5vEPdkMJY4p98LDdn6FSZfXLbd6iV971Gd7t6yG6Oft6ffqtufp-fnF6ctV0XGvZCHNbb2gBlDfARdcJ77jQXFIuW6BMKMWXLaGsFVxq0RoOUvuOt04T6qTjh-jLznecbtew7GCoh_R2TGHt0sZGF-y_yhBW9i7OlklluObV4NPeIMWfE-Ri1yF30PdugDhlywjjhitZweMd2KWYcwL_9AgldpuV3WZln7OqG3hvvRWeaWmFsFTVHCvy-T-I9VPfF3golf2wY-9ziekJZlK0knFS9Y873bto3V0K2d78YIRyQqVUqn7oL0eetHc</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>20239375</pqid></control><display><type>article</type><title>tumor suppressor activity of IKKα in stratified epithelia is exerted in part via the TGF-β antiproliferative pathway</title><source>Jstor Complete Legacy</source><source>Full-Text Journals in Chemistry (Open access)</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Marinari, Barbara ; Moretti, Francesca ; Botti, Elisabetta ; Giustizieri, Maria Laura ; Descargues, Pascal ; Giunta, Alessandro ; Stolfi, Carmine ; Ballaro, Costanza ; Papoutsaki, Marina ; Alemà, Stefano ; Monteleone, Giovanni ; Chimenti, Sergio ; Karin, Michael ; Costanzo, Antonio</creator><creatorcontrib>Marinari, Barbara ; Moretti, Francesca ; Botti, Elisabetta ; Giustizieri, Maria Laura ; Descargues, Pascal ; Giunta, Alessandro ; Stolfi, Carmine ; Ballaro, Costanza ; Papoutsaki, Marina ; Alemà, Stefano ; Monteleone, Giovanni ; Chimenti, Sergio ; Karin, Michael ; Costanzo, Antonio</creatorcontrib><description>The transforming growth factor type β-1 (TGF-β) signaling pathway is a major tumor suppressor during early carcinogenesis, and its growth-suppressive activity is commonly lost during early tumor progression. IκB kinase α (IKKα) also acts as a tumor suppressor in stratified epithelia, and its expression and nuclear localization are progressively down-regulated during malignant progression of squamous cell carcinoma (SCC) and acquisition of an invasive phenotype. A critical role for IKKα in TGF-β signaling in stratified epithelia was identified recently during normal keratinocyte differentiation, and both IKKα and components of the TGF-β signaling pathway are required for induction of antiproliferative Myc antagonists in such cells. We now describe that the interaction between IKKα and the TGF-β signaling pathway is also important in a subset of SCCs. In SCCs that are unable to shuttle IKKα to the nucleus, defective TGF-β-induced growth arrest was rescued by introduction of a constitutively nuclear IKKα variant. These results suggest that the tumor-suppressive activity of IKKα in stratified epithelia may be exerted in part via the TGF-β signaling pathway.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0809288105</identifier><identifier>PMID: 18957551</identifier><language>eng</language><publisher>National Academy of Sciences</publisher><subject>Biological Sciences ; Cell cycle ; Cell growth ; Cell lines ; Cell nucleus ; Down regulation ; Epithelial cells ; Keratinocytes ; Skin ; Tumor cell line ; Tumors</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2008-11, Vol.105 (44), p.17091-17096</ispartof><rights>Copyright 2008 The National Academy of Sciences of the United States of America</rights><rights>2008 by The National Academy of Sciences of the USA</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3885-49b0026ee7f9e34cc4fa348351356e124773d6012643584693e58fc36a801a5a3</citedby><cites>FETCH-LOGICAL-c3885-49b0026ee7f9e34cc4fa348351356e124773d6012643584693e58fc36a801a5a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/105/44.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/25465230$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/25465230$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids></links><search><creatorcontrib>Marinari, Barbara</creatorcontrib><creatorcontrib>Moretti, Francesca</creatorcontrib><creatorcontrib>Botti, Elisabetta</creatorcontrib><creatorcontrib>Giustizieri, Maria Laura</creatorcontrib><creatorcontrib>Descargues, Pascal</creatorcontrib><creatorcontrib>Giunta, Alessandro</creatorcontrib><creatorcontrib>Stolfi, Carmine</creatorcontrib><creatorcontrib>Ballaro, Costanza</creatorcontrib><creatorcontrib>Papoutsaki, Marina</creatorcontrib><creatorcontrib>Alemà, Stefano</creatorcontrib><creatorcontrib>Monteleone, Giovanni</creatorcontrib><creatorcontrib>Chimenti, Sergio</creatorcontrib><creatorcontrib>Karin, Michael</creatorcontrib><creatorcontrib>Costanzo, Antonio</creatorcontrib><title>tumor suppressor activity of IKKα in stratified epithelia is exerted in part via the TGF-β antiproliferative pathway</title><title>Proceedings of the National Academy of Sciences - PNAS</title><description>The transforming growth factor type β-1 (TGF-β) signaling pathway is a major tumor suppressor during early carcinogenesis, and its growth-suppressive activity is commonly lost during early tumor progression. IκB kinase α (IKKα) also acts as a tumor suppressor in stratified epithelia, and its expression and nuclear localization are progressively down-regulated during malignant progression of squamous cell carcinoma (SCC) and acquisition of an invasive phenotype. A critical role for IKKα in TGF-β signaling in stratified epithelia was identified recently during normal keratinocyte differentiation, and both IKKα and components of the TGF-β signaling pathway are required for induction of antiproliferative Myc antagonists in such cells. We now describe that the interaction between IKKα and the TGF-β signaling pathway is also important in a subset of SCCs. In SCCs that are unable to shuttle IKKα to the nucleus, defective TGF-β-induced growth arrest was rescued by introduction of a constitutively nuclear IKKα variant. These results suggest that the tumor-suppressive activity of IKKα in stratified epithelia may be exerted in part via the TGF-β signaling pathway.</description><subject>Biological Sciences</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>Cell lines</subject><subject>Cell nucleus</subject><subject>Down regulation</subject><subject>Epithelial cells</subject><subject>Keratinocytes</subject><subject>Skin</subject><subject>Tumor cell line</subject><subject>Tumors</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><recordid>eNqFkb9uFDEQxi0EIkegpkK4QqLYxH_XdoMURSREiURBUlvO3jjnaG-92N4l91jwIHkmfLpTIiqqGc33m88efQi9p-SIEsWPx8HlI6KJYVpTIl-gBSWGNq0w5CVaEMJUowUTB-hNzveEECM1eY0OqDZSSUkXaC7TOiacp3FMkHNtXVfCHMoGR48vLi8ff-Mw4FySK8EHWGIYQ1lBHxwOGcMDpFKHFRldKniu46ri6_Oz5vEPdkMJY4p98LDdn6FSZfXLbd6iV971Gd7t6yG6Oft6ffqtufp-fnF6ctV0XGvZCHNbb2gBlDfARdcJ77jQXFIuW6BMKMWXLaGsFVxq0RoOUvuOt04T6qTjh-jLznecbtew7GCoh_R2TGHt0sZGF-y_yhBW9i7OlklluObV4NPeIMWfE-Ri1yF30PdugDhlywjjhitZweMd2KWYcwL_9AgldpuV3WZln7OqG3hvvRWeaWmFsFTVHCvy-T-I9VPfF3golf2wY-9ziekJZlK0knFS9Y873bto3V0K2d78YIRyQqVUqn7oL0eetHc</recordid><startdate>20081104</startdate><enddate>20081104</enddate><creator>Marinari, Barbara</creator><creator>Moretti, Francesca</creator><creator>Botti, Elisabetta</creator><creator>Giustizieri, Maria Laura</creator><creator>Descargues, Pascal</creator><creator>Giunta, Alessandro</creator><creator>Stolfi, Carmine</creator><creator>Ballaro, Costanza</creator><creator>Papoutsaki, Marina</creator><creator>Alemà, Stefano</creator><creator>Monteleone, Giovanni</creator><creator>Chimenti, Sergio</creator><creator>Karin, Michael</creator><creator>Costanzo, Antonio</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>20081104</creationdate><title>tumor suppressor activity of IKKα in stratified epithelia is exerted in part via the TGF-β antiproliferative pathway</title><author>Marinari, Barbara ; Moretti, Francesca ; Botti, Elisabetta ; Giustizieri, Maria Laura ; Descargues, Pascal ; Giunta, Alessandro ; Stolfi, Carmine ; Ballaro, Costanza ; Papoutsaki, Marina ; Alemà, Stefano ; Monteleone, Giovanni ; Chimenti, Sergio ; Karin, Michael ; Costanzo, Antonio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3885-49b0026ee7f9e34cc4fa348351356e124773d6012643584693e58fc36a801a5a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Biological Sciences</topic><topic>Cell cycle</topic><topic>Cell growth</topic><topic>Cell lines</topic><topic>Cell nucleus</topic><topic>Down regulation</topic><topic>Epithelial cells</topic><topic>Keratinocytes</topic><topic>Skin</topic><topic>Tumor cell line</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Marinari, Barbara</creatorcontrib><creatorcontrib>Moretti, Francesca</creatorcontrib><creatorcontrib>Botti, Elisabetta</creatorcontrib><creatorcontrib>Giustizieri, Maria Laura</creatorcontrib><creatorcontrib>Descargues, Pascal</creatorcontrib><creatorcontrib>Giunta, Alessandro</creatorcontrib><creatorcontrib>Stolfi, Carmine</creatorcontrib><creatorcontrib>Ballaro, Costanza</creatorcontrib><creatorcontrib>Papoutsaki, Marina</creatorcontrib><creatorcontrib>Alemà, Stefano</creatorcontrib><creatorcontrib>Monteleone, Giovanni</creatorcontrib><creatorcontrib>Chimenti, Sergio</creatorcontrib><creatorcontrib>Karin, Michael</creatorcontrib><creatorcontrib>Costanzo, Antonio</creatorcontrib><collection>AGRIS</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Marinari, Barbara</au><au>Moretti, Francesca</au><au>Botti, Elisabetta</au><au>Giustizieri, Maria Laura</au><au>Descargues, Pascal</au><au>Giunta, Alessandro</au><au>Stolfi, Carmine</au><au>Ballaro, Costanza</au><au>Papoutsaki, Marina</au><au>Alemà, Stefano</au><au>Monteleone, Giovanni</au><au>Chimenti, Sergio</au><au>Karin, Michael</au><au>Costanzo, Antonio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>tumor suppressor activity of IKKα in stratified epithelia is exerted in part via the TGF-β antiproliferative pathway</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><date>2008-11-04</date><risdate>2008</risdate><volume>105</volume><issue>44</issue><spage>17091</spage><epage>17096</epage><pages>17091-17096</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>The transforming growth factor type β-1 (TGF-β) signaling pathway is a major tumor suppressor during early carcinogenesis, and its growth-suppressive activity is commonly lost during early tumor progression. IκB kinase α (IKKα) also acts as a tumor suppressor in stratified epithelia, and its expression and nuclear localization are progressively down-regulated during malignant progression of squamous cell carcinoma (SCC) and acquisition of an invasive phenotype. A critical role for IKKα in TGF-β signaling in stratified epithelia was identified recently during normal keratinocyte differentiation, and both IKKα and components of the TGF-β signaling pathway are required for induction of antiproliferative Myc antagonists in such cells. We now describe that the interaction between IKKα and the TGF-β signaling pathway is also important in a subset of SCCs. In SCCs that are unable to shuttle IKKα to the nucleus, defective TGF-β-induced growth arrest was rescued by introduction of a constitutively nuclear IKKα variant. These results suggest that the tumor-suppressive activity of IKKα in stratified epithelia may be exerted in part via the TGF-β signaling pathway.</abstract><pub>National Academy of Sciences</pub><pmid>18957551</pmid><doi>10.1073/pnas.0809288105</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2008-11, Vol.105 (44), p.17091-17096 |
| issn | 0027-8424 1091-6490 |
| language | eng |
| recordid | cdi_pnas_primary_105_44_17091 |
| source | Jstor Complete Legacy; Full-Text Journals in Chemistry (Open access); PubMed Central; Alma/SFX Local Collection |
| subjects | Biological Sciences Cell cycle Cell growth Cell lines Cell nucleus Down regulation Epithelial cells Keratinocytes Skin Tumor cell line Tumors |
| title | tumor suppressor activity of IKKα in stratified epithelia is exerted in part via the TGF-β antiproliferative pathway |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-12T02%3A06%3A36IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_pnas_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=tumor%20suppressor%20activity%20of%20IKK%CE%B1%20in%20stratified%20epithelia%20is%20exerted%20in%20part%20via%20the%20TGF-%CE%B2%20antiproliferative%20pathway&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20-%20PNAS&rft.au=Marinari,%20Barbara&rft.date=2008-11-04&rft.volume=105&rft.issue=44&rft.spage=17091&rft.epage=17096&rft.pages=17091-17096&rft.issn=0027-8424&rft.eissn=1091-6490&rft_id=info:doi/10.1073/pnas.0809288105&rft_dat=%3Cjstor_pnas_%3E25465230%3C/jstor_pnas_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=20239375&rft_id=info:pmid/18957551&rft_jstor_id=25465230&rfr_iscdi=true |