PAI-1 mediates the antiangiogenic and profibrinolytic effects of 16K prolactin.

[en] The N-terminal fragment of prolactin (16K PRL) inhibits tumor growth by impairing angiogenesis, but the underlying mechanisms are unknown. Here, we found that 16K PRL binds the fibrinolytic inhibitor plasminogen activator inhibitor-1 (PAI-1), which is known to contextually promote tumor angiogenesis and growth. Loss of PAI-1 abrogated the antitumoral and antiangiogenic effects of 16K PRL. PAI-1 bound the ternary complex PAI-1-urokinase-type plasminogen activator (uPA)-uPA receptor (uPAR), thereby exerting antiangiogenic effects. By inhibiting the antifibrinolytic activity of PAI-1, 16K PRL also protected mice against thromboembolism and promoted arterial clot lysis. Thus, by signaling through the PAI-1-uPA-uPAR complex, 16K PRL impairs tumor vascularization and growth and, by inhibiting the antifibrinolytic activity of PAI-1, promotes thrombolysis.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Bajou, Khalid ^✱; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire

Herkenne, Stéphanie ^✱; Université de Liège - ULiège > R&D Direction : Chercheurs ULiège en mobilité

Thijssen, Victor L.

D'Amico, Salvino

Nguyen, Ngoc-Quynh-Nhu

Bouche, Ann

Tabruyn, Sébastien

Srahna, Mohammed

Carabin, Jean-Yves

Nivelles, Olivier ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire

More authors (12 more)

^✱ These authors have contributed equally to this work.

Language :

English

Title :

PAI-1 mediates the antiangiogenic and profibrinolytic effects of 16K prolactin.

Publication date :

2014

Journal title :

Nature Medicine

ISSN :

1078-8956

eISSN :

1546-170X

Publisher :

Nature Publishing Group, New York, United States - New York

Volume :

(7)

Pages :

741

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

http://reflexions.ulg.ac.be/en/16KPRLthrombosis

Available on ORBi :

since 07 July 2014

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