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A novel L1CAM isoform with angiogenic activity generated by NOVA2-mediated alternative splicing

Angiolini, Francesca (author)
IRCCS, European Inst Oncol, Program Gynecol Oncol, IEO,Unit Gynecol Oncol Res, Milan, Italy;GSK Vaccines Srl, Siena, Italy
Belloni, Elisa (author)
CNR, Ist Genet Mol, Pavia, Italy
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
Forneris, Federico (author)
Univ Pavia, Dept Biol & Biotechnol, Armenise Harvard Lab Struct Biol, Pavia, Italy
Paola, Paronetto Maria (author)
Univ Roma Foro Italico, Dept Movement Human & Hlth Sci, Rome, Italy
Lupia, Michela (author)
IRCCS, European Inst Oncol, Program Gynecol Oncol, IEO,Unit Gynecol Oncol Res, Milan, Italy
Brandas, Chiara (author)
CNR, Ist Genet Mol, Pavia, Italy
Pradella, Davide (author)
CNR, Ist Genet Mol, Pavia, Italy;Univ Pavia, Pavia, Italy
Di Matteo, Anna (author)
CNR, Ist Genet Mol, Pavia, Italy
Giampietro, Costanza (author)
FIRC Inst Mol Oncol, Milan, Italy;Swiss Fed Inst Technol, Dept Mech & Proc Engn, Lab Thermodynam Emerging Technol, Zurich, Switzerland
Jodice, Giovanna (author)
IRCCS, Mol Med Program, IEO, European Inst Oncol, Milan, Italy
Luise, Chiara (author)
IRCCS, Mol Med Program, IEO, European Inst Oncol, Milan, Italy
Bertalot, Giovanni (author)
IRCCS, Mol Med Program, IEO, European Inst Oncol, Milan, Italy
Freddi, Stefano (author)
IRCCS, Mol Med Program, IEO, European Inst Oncol, Milan, Italy
Malinverno, Matteo (author)
FIRC Inst Mol Oncol, Milan, Italy
Irimia, Manuel (author)
Barcelona Inst Sci & Technol, Ctr Genom Regulat, Barcelona, Spain;Univ Pompeu Fabra, Barcelona, Spain;Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain
Moulton, Jon D. (author)
Gene Tools LLC, Philomath, OR USA
Summerton, James (author)
Gene Tools LLC, Philomath, OR USA
Chiapparino, Antonella (author)
Univ Pavia, Dept Biol & Biotechnol, Armenise Harvard Lab Struct Biol, Pavia, Italy
Ghilardi, Carmen (author)
IRCCS, Ist Ric Farmacol Mario Negri, Lab Biol & Treatment Metastasis, Milan, Italy
Giavazzi, Raffaella (author)
IRCCS, Ist Ric Farmacol Mario Negri, Lab Biol & Treatment Metastasis, Milan, Italy
Nyqvist, Daniel (author)
Karolinska Institutet
Gabellini, Davide (author)
IRCCS, San Raffaele Sci Inst, Div Genet & Cell Biol, Milan, Italy
Dejana, Elisabetta (author)
Uppsala universitet,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab,FIRC Inst Mol Oncol, Milan, Italy
Cavallaro, Ugo (author)
IRCCS, European Inst Oncol, Program Gynecol Oncol, IEO,Unit Gynecol Oncol Res, Milan, Italy
Ghigna, Claudia (author)
CNR, Ist Genet Mol, Pavia, Italy
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 (creator_code:org_t)
2019
2019
English.
In: eLIFE. - 2050-084X. ; 8
Related links:
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  • Journal article (peer-reviewed)
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)

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