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

F Angiolini, E Belloni, M Giordano, M Campioni, F Forneris, PM Paola, M Lupia, C Brandas, D Pradella, A Di Matteo, C Giampietro, G Jodice, C Luise, G Bertalot, S Freddi, M Malinverno, M Irimia, JD Moulton, J Summerton, A ChiapparinoC Ghilardi, R Giavazzi, D Nyqvist, D Gabellini, E Dejana, U Cavallaro, C Ghigna

Research output: Contribution to journalArticle

Abstract

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. © 2019, Angiolini et al.
Original languageEnglish
Pages (from-to)e44305
JournaleLife
Volume8
DOIs
Publication statusPublished - 2019

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    Angiolini, F., Belloni, E., Giordano, M., Campioni, M., Forneris, F., Paola, PM., Lupia, M., Brandas, C., Pradella, D., Di Matteo, A., Giampietro, C., Jodice, G., Luise, C., Bertalot, G., Freddi, S., Malinverno, M., Irimia, M., Moulton, JD., Summerton, J., ... Ghigna, C. (2019). A novel L1CAM isoform with angiogenic activity generated by NOVA2-mediated alternative splicing: eLife. eLife, 8, e44305. https://doi.org/10.7554/eLife.44305