The hidden role of paxillin: localization to nucleus promotes tumor angiogenesis
Paxillin (PXN), a key component of the focal adhesion complex, has been associated with cancer progression, but the underlying mechanisms are poorly understood. The purpose of this study was to elucidate mechanisms by which PXN affects cancer growth and progression, which we addressed using cancer p...
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| Veröffentlicht in: | Oncogene 2021-01, Vol.40 (2), p.384-395 |
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| creator | Noh, Kyunghee Bach, Duc-Hiep Choi, Hyun-Jin Kim, Mark S. Wu, Sherry Y. Pradeep, Sunila Ivan, Cristina Cho, Min-Soon Bayraktar, Emine Rodriguez-Aguayo, Cristian Dasari, Santosh K. Stur, Elaine Mangala, Lingegowda S. Lopez-Berestein, Gabriel Sood, Anil K. |
| description | Paxillin (PXN), a key component of the focal adhesion complex, has been associated with cancer progression, but the underlying mechanisms are poorly understood. The purpose of this study was to elucidate mechanisms by which PXN affects cancer growth and progression, which we addressed using cancer patient data, cell lines, and orthotopic mouse models. We demonstrated a previously unrecognized mechanism whereby nuclear PXN enhances angiogenesis by transcriptionally regulating SRC expression. SRC, in turn, increases PLAT expression through NF-ĸB activation; PLAT promotes angiogenesis
via
LRP1 in endothelial cells. PXN silencing in ovarian cancer mouse models reduced angiogenesis, tumor growth, and metastasis. These findings provide a new understanding of the role of PXN in regulating tumor angiogenesis and growth. |
| doi_str_mv | 10.1038/s41388-020-01517-3 |
| format | Article |
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via
LRP1 in endothelial cells. PXN silencing in ovarian cancer mouse models reduced angiogenesis, tumor growth, and metastasis. These findings provide a new understanding of the role of PXN in regulating tumor angiogenesis and growth.</description><identifier>ISSN: 0950-9232</identifier><identifier>ISSN: 1476-5594</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/s41388-020-01517-3</identifier><identifier>PMID: 33149280</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>38/1 ; 42/89 ; 631/67/1517/1709 ; 631/67/2328 ; Angiogenesis ; Animal models ; Animals ; Apoptosis ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Cancer ; Carcinogenesis ; Carrier proteins ; Cell Biology ; Cell Nucleus - metabolism ; Cell Proliferation ; Disease Progression ; Endothelial cells ; Female ; Gene expression ; Gene Expression Regulation, Neoplastic ; Genetic aspects ; Health aspects ; Human Genetics ; Humans ; Internal Medicine ; Localization ; Medicine ; Medicine & Public Health ; Metastases ; Mice ; Mice, Nude ; Neovascularization ; Neovascularization, Pathologic - genetics ; Neovascularization, Pathologic - metabolism ; Neovascularization, Pathologic - pathology ; Oncology ; Ovarian cancer ; Ovarian Neoplasms - blood supply ; Ovarian Neoplasms - genetics ; Ovarian Neoplasms - metabolism ; Paxillin ; Paxillin - antagonists & inhibitors ; Paxillin - genetics ; Paxillin - metabolism ; Prognosis ; src-Family Kinases - genetics ; src-Family Kinases - metabolism ; Survival Rate ; Tissue Plasminogen Activator - genetics ; Tissue Plasminogen Activator - metabolism ; Transcription ; Tumor cell lines ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays</subject><ispartof>Oncogene, 2021-01, Vol.40 (2), p.384-395</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Limited 2020</rights><rights>COPYRIGHT 2021 Nature Publishing Group</rights><rights>The Author(s), under exclusive licence to Springer Nature Limited 2020.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c607t-111fe7e3bb72f4a52d37fbb7be3765b438d6efb148336daafb885027294d7c173</citedby><cites>FETCH-LOGICAL-c607t-111fe7e3bb72f4a52d37fbb7be3765b438d6efb148336daafb885027294d7c173</cites><orcidid>0000-0002-4848-0168 ; 0000-0002-7880-7723 ; 0000-0003-4242-1762 ; 0000-0002-9826-3137</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41388-020-01517-3$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41388-020-01517-3$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33149280$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Noh, Kyunghee</creatorcontrib><creatorcontrib>Bach, Duc-Hiep</creatorcontrib><creatorcontrib>Choi, Hyun-Jin</creatorcontrib><creatorcontrib>Kim, Mark S.</creatorcontrib><creatorcontrib>Wu, Sherry Y.</creatorcontrib><creatorcontrib>Pradeep, Sunila</creatorcontrib><creatorcontrib>Ivan, Cristina</creatorcontrib><creatorcontrib>Cho, Min-Soon</creatorcontrib><creatorcontrib>Bayraktar, Emine</creatorcontrib><creatorcontrib>Rodriguez-Aguayo, Cristian</creatorcontrib><creatorcontrib>Dasari, Santosh K.</creatorcontrib><creatorcontrib>Stur, Elaine</creatorcontrib><creatorcontrib>Mangala, Lingegowda S.</creatorcontrib><creatorcontrib>Lopez-Berestein, Gabriel</creatorcontrib><creatorcontrib>Sood, Anil K.</creatorcontrib><title>The hidden role of paxillin: localization to nucleus promotes tumor angiogenesis</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>Paxillin (PXN), a key component of the focal adhesion complex, has been associated with cancer progression, but the underlying mechanisms are poorly understood. The purpose of this study was to elucidate mechanisms by which PXN affects cancer growth and progression, which we addressed using cancer patient data, cell lines, and orthotopic mouse models. We demonstrated a previously unrecognized mechanism whereby nuclear PXN enhances angiogenesis by transcriptionally regulating SRC expression. SRC, in turn, increases PLAT expression through NF-ĸB activation; PLAT promotes angiogenesis
via
LRP1 in endothelial cells. PXN silencing in ovarian cancer mouse models reduced angiogenesis, tumor growth, and metastasis. 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Noh, Kyunghee</au><au>Bach, Duc-Hiep</au><au>Choi, Hyun-Jin</au><au>Kim, Mark S.</au><au>Wu, Sherry Y.</au><au>Pradeep, Sunila</au><au>Ivan, Cristina</au><au>Cho, Min-Soon</au><au>Bayraktar, Emine</au><au>Rodriguez-Aguayo, Cristian</au><au>Dasari, Santosh K.</au><au>Stur, Elaine</au><au>Mangala, Lingegowda S.</au><au>Lopez-Berestein, Gabriel</au><au>Sood, Anil K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The hidden role of paxillin: localization to nucleus promotes tumor angiogenesis</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><addtitle>Oncogene</addtitle><date>2021-01-14</date><risdate>2021</risdate><volume>40</volume><issue>2</issue><spage>384</spage><epage>395</epage><pages>384-395</pages><issn>0950-9232</issn><issn>1476-5594</issn><eissn>1476-5594</eissn><abstract>Paxillin (PXN), a key component of the focal adhesion complex, has been associated with cancer progression, but the underlying mechanisms are poorly understood. 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via
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| ispartof | Oncogene, 2021-01, Vol.40 (2), p.384-395 |
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| language | eng |
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| subjects | 38/1 42/89 631/67/1517/1709 631/67/2328 Angiogenesis Animal models Animals Apoptosis Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Cancer Carcinogenesis Carrier proteins Cell Biology Cell Nucleus - metabolism Cell Proliferation Disease Progression Endothelial cells Female Gene expression Gene Expression Regulation, Neoplastic Genetic aspects Health aspects Human Genetics Humans Internal Medicine Localization Medicine Medicine & Public Health Metastases Mice Mice, Nude Neovascularization Neovascularization, Pathologic - genetics Neovascularization, Pathologic - metabolism Neovascularization, Pathologic - pathology Oncology Ovarian cancer Ovarian Neoplasms - blood supply Ovarian Neoplasms - genetics Ovarian Neoplasms - metabolism Paxillin Paxillin - antagonists & inhibitors Paxillin - genetics Paxillin - metabolism Prognosis src-Family Kinases - genetics src-Family Kinases - metabolism Survival Rate Tissue Plasminogen Activator - genetics Tissue Plasminogen Activator - metabolism Transcription Tumor cell lines Tumor Cells, Cultured Xenograft Model Antitumor Assays |
| title | The hidden role of paxillin: localization to nucleus promotes tumor angiogenesis |
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