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

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.

journal_name

Elife

journal_title

eLife

authors

Angiolini F,Belloni E,Giordano M,Campioni M,Forneris F,Paronetto MP,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,Chiapparino

doi

10.7554/eLife.44305

subject

Has Abstract

pub_date

2019-03-04 00:00:00

issn

2050-084X

pii

44305

journal_volume

8

pub_type

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