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  • Angiolini, FrancescaIRCCS, European Inst Oncol, Program Gynecol Oncol, IEO,Unit Gynecol Oncol Res, Milan, Italy;GSK Vaccines Srl, Siena, Italy (author)

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

  • Article/chapterEnglish2019

Publisher, publication year, extent ...

  • 2019
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-379331
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-379331URI
  • https://doi.org/10.7554/eLife.44305DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:140414486URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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 and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Belloni, ElisaCNR, Ist Genet Mol, Pavia, Italy (author)
  • Giordano, MarcoIRCCS, European Inst Oncol, Program Gynecol Oncol, IEO,Unit Gynecol Oncol Res, Milan, Italy (author)
  • Campioni, MatteoUniv Pavia, Dept Biol & Biotechnol, Armenise Harvard Lab Struct Biol, Pavia, Italy (author)
  • Forneris, FedericoUniv Pavia, Dept Biol & Biotechnol, Armenise Harvard Lab Struct Biol, Pavia, Italy (author)
  • Paola, Paronetto MariaUniv Roma Foro Italico, Dept Movement Human & Hlth Sci, Rome, Italy (author)
  • Lupia, MichelaIRCCS, European Inst Oncol, Program Gynecol Oncol, IEO,Unit Gynecol Oncol Res, Milan, Italy (author)
  • Brandas, ChiaraCNR, Ist Genet Mol, Pavia, Italy (author)
  • Pradella, DavideCNR, Ist Genet Mol, Pavia, Italy;Univ Pavia, Pavia, Italy (author)
  • Di Matteo, AnnaCNR, Ist Genet Mol, Pavia, Italy (author)
  • Giampietro, CostanzaFIRC Inst Mol Oncol, Milan, Italy;Swiss Fed Inst Technol, Dept Mech & Proc Engn, Lab Thermodynam Emerging Technol, Zurich, Switzerland (author)
  • Jodice, GiovannaIRCCS, Mol Med Program, IEO, European Inst Oncol, Milan, Italy (author)
  • Luise, ChiaraIRCCS, Mol Med Program, IEO, European Inst Oncol, Milan, Italy (author)
  • Bertalot, GiovanniIRCCS, Mol Med Program, IEO, European Inst Oncol, Milan, Italy (author)
  • Freddi, StefanoIRCCS, Mol Med Program, IEO, European Inst Oncol, Milan, Italy (author)
  • Malinverno, MatteoFIRC Inst Mol Oncol, Milan, Italy (author)
  • Irimia, ManuelBarcelona Inst Sci & Technol, Ctr Genom Regulat, Barcelona, Spain;Univ Pompeu Fabra, Barcelona, Spain;Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain (author)
  • Moulton, Jon D.Gene Tools LLC, Philomath, OR USA (author)
  • Summerton, JamesGene Tools LLC, Philomath, OR USA (author)
  • Chiapparino, AntonellaUniv Pavia, Dept Biol & Biotechnol, Armenise Harvard Lab Struct Biol, Pavia, Italy (author)
  • Ghilardi, CarmenIRCCS, Ist Ric Farmacol Mario Negri, Lab Biol & Treatment Metastasis, Milan, Italy (author)
  • Giavazzi, RaffaellaIRCCS, Ist Ric Farmacol Mario Negri, Lab Biol & Treatment Metastasis, Milan, Italy (author)
  • Nyqvist, DanielKarolinska Institutet (author)
  • Gabellini, DavideIRCCS, San Raffaele Sci Inst, Div Genet & Cell Biol, Milan, Italy (author)
  • Dejana, ElisabettaUppsala universitet,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab,FIRC Inst Mol Oncol, Milan, Italy(Swepub:uu)elide443 (author)
  • Cavallaro, UgoIRCCS, European Inst Oncol, Program Gynecol Oncol, IEO,Unit Gynecol Oncol Res, Milan, Italy (author)
  • Ghigna, ClaudiaCNR, Ist Genet Mol, Pavia, Italy (author)
  • IRCCS, European Inst Oncol, Program Gynecol Oncol, IEO,Unit Gynecol Oncol Res, Milan, Italy;GSK Vaccines Srl, Siena, ItalyCNR, Ist Genet Mol, Pavia, Italy (creator_code:org_t)

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