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LPHN2 inhibits vascular permeability by differential control of endothelial cell adhesion.
Camillo, Chiara; Facchinello, Nicola; Villari, Giulia; Mana, Giulia; Gioelli, Noemi; Sandri, Chiara; Astone, Matteo; Tortarolo, Dora; Clapero, Fabiana; Gays, Dafne; Oberkersch, Roxana E; Arese, Marco; Tamagnone, Luca; Valdembri, Donatella; Santoro, Massimo M; Serini, Guido.
Afiliación
  • Camillo C; Candiolo Cancer Institute-Fondazione del Piemonte per l'Oncologia, Istituto di Ricovero e Cura a Carattere Scientifico, Candiolo, Italy.
  • Facchinello N; Department of Oncology, University of Torino School of Medicine, Candiolo, Italy.
  • Villari G; Laboratory of Angiogenesis and Cancer Metabolism, Department of Biology, University of Padova, Padova, Italy.
  • Mana G; Candiolo Cancer Institute-Fondazione del Piemonte per l'Oncologia, Istituto di Ricovero e Cura a Carattere Scientifico, Candiolo, Italy.
  • Gioelli N; Department of Oncology, University of Torino School of Medicine, Candiolo, Italy.
  • Sandri C; Candiolo Cancer Institute-Fondazione del Piemonte per l'Oncologia, Istituto di Ricovero e Cura a Carattere Scientifico, Candiolo, Italy.
  • Astone M; Department of Oncology, University of Torino School of Medicine, Candiolo, Italy.
  • Tortarolo D; Candiolo Cancer Institute-Fondazione del Piemonte per l'Oncologia, Istituto di Ricovero e Cura a Carattere Scientifico, Candiolo, Italy.
  • Clapero F; Department of Oncology, University of Torino School of Medicine, Candiolo, Italy.
  • Gays D; Candiolo Cancer Institute-Fondazione del Piemonte per l'Oncologia, Istituto di Ricovero e Cura a Carattere Scientifico, Candiolo, Italy.
  • Oberkersch RE; Department of Oncology, University of Torino School of Medicine, Candiolo, Italy.
  • Arese M; Laboratory of Angiogenesis and Cancer Metabolism, Department of Biology, University of Padova, Padova, Italy.
  • Tamagnone L; Candiolo Cancer Institute-Fondazione del Piemonte per l'Oncologia, Istituto di Ricovero e Cura a Carattere Scientifico, Candiolo, Italy.
  • Valdembri D; Department of Oncology, University of Torino School of Medicine, Candiolo, Italy.
  • Santoro MM; Candiolo Cancer Institute-Fondazione del Piemonte per l'Oncologia, Istituto di Ricovero e Cura a Carattere Scientifico, Candiolo, Italy.
  • Serini G; Department of Oncology, University of Torino School of Medicine, Candiolo, Italy.
J Cell Biol ; 220(11)2021 11 01.
Article en En | MEDLINE | ID: mdl-34581723
Dynamic modulation of endothelial cell-to-cell and cell-to-extracellular matrix (ECM) adhesion is essential for blood vessel patterning and functioning. Yet the molecular mechanisms involved in this process have not been completely deciphered. We identify the adhesion G protein-coupled receptor (ADGR) Latrophilin 2 (LPHN2) as a novel determinant of endothelial cell (EC) adhesion and barrier function. In cultured ECs, endogenous LPHN2 localizes at ECM contacts, signals through cAMP/Rap1, and inhibits focal adhesion (FA) formation and nuclear localization of YAP/TAZ transcriptional regulators, while promoting tight junction (TJ) assembly. ECs also express an endogenous LPHN2 ligand, fibronectin leucine-rich transmembrane 2 (FLRT2), that prevents ECM-elicited EC behaviors in an LPHN2-dependent manner. Vascular ECs of lphn2a knock-out zebrafish embryos become abnormally stretched, display a hyperactive YAP/TAZ pathway, and lack proper intercellular TJs. Consistently, blood vessels are hyperpermeable, and intravascularly injected cancer cells extravasate more easily in lphn2a null animals. Thus, LPHN2 ligands, such as FLRT2, may be therapeutically exploited to interfere with cancer metastatic dissemination.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Permeabilidad Capilar / Endotelio Vascular / Adhesión Celular / Receptores Acoplados a Proteínas G / Células Endoteliales de la Vena Umbilical Humana Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: J Cell Biol Año: 2021 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos
Texto completo
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Permeabilidad Capilar / Endotelio Vascular / Adhesión Celular / Receptores Acoplados a Proteínas G / Células Endoteliales de la Vena Umbilical Humana Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: J Cell Biol Año: 2021 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos