| Autor: |
Francesca Angiolini, Elisa Belloni, Marco Giordano, Matteo Campioni, Federico Forneris, Maria Paola Paronetto, Michela Lupia, Chiara Brandas, Davide Pradella, Anna Di Matteo, Costanza Giampietro, Giovanna Jodice, Chiara Luise, Giovanni Bertalot, Stefano Freddi, Matteo Malinverno, Manuel Irimia, Jon D Moulton, James Summerton, Antonella Chiapparino, Carmen Ghilardi, Raffaella Giavazzi, Daniel Nyqvist, Davide Gabellini, Elisabetta Dejana, Ugo Cavallaro, Claudia Ghigna |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
eLife, Vol 8 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2050-084X |
| DOI: |
10.7554/eLife.44305 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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