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NeuroD1 regulates survival and migration of neuroendocrine lung carcinomas via signaling molecules TrkB and NCAM
Small-cell lung cancer and other aggressive neuroendocrine cancers are often associated with early dissemination and frequent metastases. We demonstrate that neurogenic differentiation 1 (NeuroD1) is a regulatory hub securing cross talk among survival and migratory-inducing signaling pathways in neu...
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| Published in: | Proceedings of the National Academy of Sciences - PNAS 2013-04, Vol.110 (16), p.6524-6529 |
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| Main Authors: | , , , , , , , , , , |
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| cited_by | cdi_FETCH-LOGICAL-c533t-26b2003c2d8baeb04e57866c03065427c5caaa146935dd9733459084286110f93 |
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| cites | cdi_FETCH-LOGICAL-c533t-26b2003c2d8baeb04e57866c03065427c5caaa146935dd9733459084286110f93 |
| container_end_page | 6529 |
| container_issue | 16 |
| container_start_page | 6524 |
| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 110 |
| creator | Osborne, Jihan K. Larsen, Jill E. Shields, Misty D. Gonzales, Joshua X. Shames, David S. Sato, Mitsuo Kulkarni, Ashwinikumar Wistuba, Ignacio I. Girard, Luc Minna, John D. Cobb, Melanie H. |
| description | Small-cell lung cancer and other aggressive neuroendocrine cancers are often associated with early dissemination and frequent metastases. We demonstrate that neurogenic differentiation 1 (NeuroD1) is a regulatory hub securing cross talk among survival and migratory-inducing signaling pathways in neuroendocrine lung carcinomas. We find that NeuroD1 promotes tumor cell survival and metastasis in aggressive neuroendocrine lung tumors through regulation of the receptor tyrosine kinase tropomyosinrelated kinase B (TrkB). Like TrkB, the prometastatic signaling molecule neural cell adhesion molecule (NCAM) is a downstream target of NeuroD1, whose impaired expression mirrors loss of NeuroD1. TrkB and NCAM may be therapeutic targets for aggressive neuroendocrine cancers that express NeuroD1. |
| doi_str_mv | 10.1073/pnas.1303932110 |
| format | article |
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We demonstrate that neurogenic differentiation 1 (NeuroD1) is a regulatory hub securing cross talk among survival and migratory-inducing signaling pathways in neuroendocrine lung carcinomas. We find that NeuroD1 promotes tumor cell survival and metastasis in aggressive neuroendocrine lung tumors through regulation of the receptor tyrosine kinase tropomyosinrelated kinase B (TrkB). Like TrkB, the prometastatic signaling molecule neural cell adhesion molecule (NCAM) is a downstream target of NeuroD1, whose impaired expression mirrors loss of NeuroD1. TrkB and NCAM may be therapeutic targets for aggressive neuroendocrine cancers that express NeuroD1.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1303932110</identifier><identifier>PMID: 23553831</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Analysis of Variance ; Animals ; Basic Helix-Loop-Helix Transcription Factors - metabolism ; Biological Sciences ; Carbazoles ; Cell adhesion & migration ; Cell Line, Tumor ; Cell lines ; Cell Movement - physiology ; Cell Survival - physiology ; Chromatin Immunoprecipitation ; DNA Primers - genetics ; Epithelial cells ; Humans ; Immunoblotting ; Immunoprecipitation ; Kinases ; Luciferases ; Lung cancer ; Lung neoplasms ; Lung Neoplasms - metabolism ; Lung Neoplasms - physiopathology ; Lungs ; Metastasis ; Mice ; Microarray Analysis ; Neural cell adhesion molecules ; Neural Cell Adhesion Molecules - metabolism ; Neuroendocrine carcinoma ; Neurons ; Plasmids - genetics ; Real-Time Polymerase Chain Reaction ; Receptor, trkB - metabolism ; Signal transduction ; Small Cell Lung Carcinoma - metabolism ; Small Cell Lung Carcinoma - physiopathology ; Tumor cell line ; Tumors</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2013-04, Vol.110 (16), p.6524-6529</ispartof><rights>copyright © 1993-2008 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Apr 16, 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c533t-26b2003c2d8baeb04e57866c03065427c5caaa146935dd9733459084286110f93</citedby><cites>FETCH-LOGICAL-c533t-26b2003c2d8baeb04e57866c03065427c5caaa146935dd9733459084286110f93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/110/16.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/42590452$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/42590452$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793,58238,58471</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23553831$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Osborne, Jihan K.</creatorcontrib><creatorcontrib>Larsen, Jill E.</creatorcontrib><creatorcontrib>Shields, Misty D.</creatorcontrib><creatorcontrib>Gonzales, Joshua X.</creatorcontrib><creatorcontrib>Shames, David S.</creatorcontrib><creatorcontrib>Sato, Mitsuo</creatorcontrib><creatorcontrib>Kulkarni, Ashwinikumar</creatorcontrib><creatorcontrib>Wistuba, Ignacio I.</creatorcontrib><creatorcontrib>Girard, Luc</creatorcontrib><creatorcontrib>Minna, John D.</creatorcontrib><creatorcontrib>Cobb, Melanie H.</creatorcontrib><title>NeuroD1 regulates survival and migration of neuroendocrine lung carcinomas via signaling molecules TrkB and NCAM</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Small-cell lung cancer and other aggressive neuroendocrine cancers are often associated with early dissemination and frequent metastases. We demonstrate that neurogenic differentiation 1 (NeuroD1) is a regulatory hub securing cross talk among survival and migratory-inducing signaling pathways in neuroendocrine lung carcinomas. We find that NeuroD1 promotes tumor cell survival and metastasis in aggressive neuroendocrine lung tumors through regulation of the receptor tyrosine kinase tropomyosinrelated kinase B (TrkB). Like TrkB, the prometastatic signaling molecule neural cell adhesion molecule (NCAM) is a downstream target of NeuroD1, whose impaired expression mirrors loss of NeuroD1. 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We demonstrate that neurogenic differentiation 1 (NeuroD1) is a regulatory hub securing cross talk among survival and migratory-inducing signaling pathways in neuroendocrine lung carcinomas. We find that NeuroD1 promotes tumor cell survival and metastasis in aggressive neuroendocrine lung tumors through regulation of the receptor tyrosine kinase tropomyosinrelated kinase B (TrkB). Like TrkB, the prometastatic signaling molecule neural cell adhesion molecule (NCAM) is a downstream target of NeuroD1, whose impaired expression mirrors loss of NeuroD1. TrkB and NCAM may be therapeutic targets for aggressive neuroendocrine cancers that express NeuroD1.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>23553831</pmid><doi>10.1073/pnas.1303932110</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2013-04, Vol.110 (16), p.6524-6529 |
| issn | 0027-8424 1091-6490 |
| language | eng |
| recordid | cdi_proquest_journals_1329184681 |
| source | JSTOR Archival Journals and Primary Sources Collection; PubMed Central |
| subjects | Analysis of Variance Animals Basic Helix-Loop-Helix Transcription Factors - metabolism Biological Sciences Carbazoles Cell adhesion & migration Cell Line, Tumor Cell lines Cell Movement - physiology Cell Survival - physiology Chromatin Immunoprecipitation DNA Primers - genetics Epithelial cells Humans Immunoblotting Immunoprecipitation Kinases Luciferases Lung cancer Lung neoplasms Lung Neoplasms - metabolism Lung Neoplasms - physiopathology Lungs Metastasis Mice Microarray Analysis Neural cell adhesion molecules Neural Cell Adhesion Molecules - metabolism Neuroendocrine carcinoma Neurons Plasmids - genetics Real-Time Polymerase Chain Reaction Receptor, trkB - metabolism Signal transduction Small Cell Lung Carcinoma - metabolism Small Cell Lung Carcinoma - physiopathology Tumor cell line Tumors |
| title | NeuroD1 regulates survival and migration of neuroendocrine lung carcinomas via signaling molecules TrkB and NCAM |
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