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A novel L1CAM isofo...
A novel L1CAM isoform with angiogenic activity generated by NOVA2-mediated alternative splicing
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- Angiolini, Francesca (author)
- IRCCS, European Inst Oncol, Program Gynecol Oncol, IEO,Unit Gynecol Oncol Res, Milan, Italy;GSK Vaccines Srl, Siena, Italy
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- Belloni, Elisa (author)
- CNR, Ist Genet Mol, Pavia, Italy
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- Giordano, Marco (author)
- IRCCS, European Inst Oncol, Program Gynecol Oncol, IEO,Unit Gynecol Oncol Res, Milan, Italy
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- Campioni, Matteo (author)
- Univ Pavia, Dept Biol & Biotechnol, Armenise Harvard Lab Struct Biol, Pavia, Italy
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- Forneris, Federico (author)
- Univ Pavia, Dept Biol & Biotechnol, Armenise Harvard Lab Struct Biol, Pavia, Italy
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- Paola, Paronetto Maria (author)
- Univ Roma Foro Italico, Dept Movement Human & Hlth Sci, Rome, Italy
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- Lupia, Michela (author)
- IRCCS, European Inst Oncol, Program Gynecol Oncol, IEO,Unit Gynecol Oncol Res, Milan, Italy
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- Brandas, Chiara (author)
- CNR, Ist Genet Mol, Pavia, Italy
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- Pradella, Davide (author)
- CNR, Ist Genet Mol, Pavia, Italy;Univ Pavia, Pavia, Italy
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- Di Matteo, Anna (author)
- CNR, Ist Genet Mol, Pavia, Italy
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- Giampietro, Costanza (author)
- FIRC Inst Mol Oncol, Milan, Italy;Swiss Fed Inst Technol, Dept Mech & Proc Engn, Lab Thermodynam Emerging Technol, Zurich, Switzerland
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- Jodice, Giovanna (author)
- IRCCS, Mol Med Program, IEO, European Inst Oncol, Milan, Italy
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- Luise, Chiara (author)
- IRCCS, Mol Med Program, IEO, European Inst Oncol, Milan, Italy
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- Bertalot, Giovanni (author)
- IRCCS, Mol Med Program, IEO, European Inst Oncol, Milan, Italy
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- Freddi, Stefano (author)
- IRCCS, Mol Med Program, IEO, European Inst Oncol, Milan, Italy
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- Malinverno, Matteo (author)
- FIRC Inst Mol Oncol, Milan, Italy
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- Irimia, Manuel (author)
- Barcelona Inst Sci & Technol, Ctr Genom Regulat, Barcelona, Spain;Univ Pompeu Fabra, Barcelona, Spain;Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain
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- Moulton, Jon D. (author)
- Gene Tools LLC, Philomath, OR USA
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- Summerton, James (author)
- Gene Tools LLC, Philomath, OR USA
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- Chiapparino, Antonella (author)
- Univ Pavia, Dept Biol & Biotechnol, Armenise Harvard Lab Struct Biol, Pavia, Italy
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- Ghilardi, Carmen (author)
- IRCCS, Ist Ric Farmacol Mario Negri, Lab Biol & Treatment Metastasis, Milan, Italy
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- Giavazzi, Raffaella (author)
- IRCCS, Ist Ric Farmacol Mario Negri, Lab Biol & Treatment Metastasis, Milan, Italy
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- Nyqvist, Daniel (author)
- Karolinska Institutet
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- Gabellini, Davide (author)
- IRCCS, San Raffaele Sci Inst, Div Genet & Cell Biol, Milan, Italy
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- Dejana, Elisabetta (author)
- Uppsala universitet,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab,FIRC Inst Mol Oncol, Milan, Italy
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- Cavallaro, Ugo (author)
- IRCCS, European Inst Oncol, Program Gynecol Oncol, IEO,Unit Gynecol Oncol Res, Milan, Italy
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- Ghigna, Claudia (author)
- CNR, Ist Genet Mol, Pavia, Italy
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(creator_code:org_t)
- 2019
- 2019
- English.
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In: eLIFE. - 2050-084X. ; 8
- Related links:
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https://doi.org/10.7...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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Abstract
Subject headings
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- The biological players involved in angiogenesis are only partially defined. Here, we report that endothelial cells (ECs) express a novel isoform of the cell-surface adhesion molecule L1CAM, termed L1-ΔTM. The splicing factor NOVA2, which binds directly to L1CAM pre-mRNA, is necessary and sufficient for the skipping of L1CAM transmembrane domain in ECs, leading to the release of soluble L1-ΔTM. The latter exerts high angiogenic function through both autocrine and paracrine activities. Mechanistically, L1-ΔTM-induced angiogenesis requires fibroblast growth factor receptor-1 signaling, implying a crosstalk between the two molecules. NOVA2 and L1-ΔTM are overexpressed in the vasculature of ovarian cancer, where L1-ΔTM levels correlate with tumor vascularization, supporting the involvement of NOVA2-mediated L1-ΔTM production in tumor angiogenesis. Finally, high NOVA2 expression is associated with poor outcome in ovarian cancer patients. Our results point to L1-ΔTM as a novel, EC-derived angiogenic factor which may represent a target for innovative antiangiogenic therapies.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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eLIFE
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- By the author/editor
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Angiolini, Franc ...
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Belloni, Elisa
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Giordano, Marco
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Campioni, Matteo
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Forneris, Federi ...
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Paola, Paronetto ...
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show more...
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Lupia, Michela
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Brandas, Chiara
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Pradella, Davide
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Di Matteo, Anna
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Giampietro, Cost ...
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Jodice, Giovanna
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Luise, Chiara
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Bertalot, Giovan ...
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Freddi, Stefano
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Malinverno, Matt ...
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Irimia, Manuel
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Moulton, Jon D.
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Summerton, James
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Chiapparino, Ant ...
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Ghilardi, Carmen
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Giavazzi, Raffae ...
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Nyqvist, Daniel
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Gabellini, David ...
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Dejana, Elisabet ...
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Cavallaro, Ugo
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Ghigna, Claudia
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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eLIFE
- By the university
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Uppsala University
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Karolinska Institutet