H-Prune through GSK-3β interaction sustains canonical WNT/β-catenin signaling enhancing cancer progression in NSCLC

• Published in: Oncotarget 2014-07, Vol.5 (14), p.5736-5749
• Main Authors: Carotenuto, Marianeve, De Antonellis, Pasqualino, Liguori, Lucia, Benvenuto, Giovanna, Magliulo, Daniela, Alonzi, Alessandro, Turino, Cecilia, Attanasio, Carmela, Damiani, Valentina, Bello, Anna Maria, Vitiello, Fabiana, Pasquinelli, Rosa, Terracciano, Luigi, Federico, Antonella, Fusco, Alfredo, Freeman, Jamie, Dale, Trevor C, Decraene, Charles, Chiappetta, Gennaro, Piantedosi, Francovito, Calabrese, Cecilia, Zollo, Massimo
• Format: Article
• Language: English
• Subjects: Animals; beta Catenin - genetics; beta Catenin - metabolism; Carcinoma, Non-Small-Cell Lung - enzymology; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Carrier Proteins - blood; Carrier Proteins - genetics; Disease Progression; Female; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; Heterografts; Humans; Lung Neoplasms - enzymology; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Mice; Mice, Nude; Phosphoric Monoester Hydrolases; Research Paper; Wnt Signaling Pathway
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.2169

H-Prune hydrolyzes short-chain polyphosphates (PPase activity) together with an hitherto cAMP-phosphodiesterase (PDE), the latest influencing different human cancers by its overexpression. H-Prune promotes cell migration in cooperation with glycogen synthase kinase-3 (Gsk-3β). Gsk-3β is a negative regulator of canonical WNT/β-catenin signaling. Here, we investigate the role of Gsk-3β/h-Prune complex in the regulation of WNT/β-catenin signaling, demonstrating the h-Prune capability to activate WNT signaling also in a paracrine manner, through Wnt3a secretion. In vivo study demonstrates that h-Prune silencing inhibits lung metastasis formation, increasing mouse survival. We assessed h-Prune levels in peripheral blood of lung cancer patients using ELISA assay, showing that h-Prune is an early diagnostic marker for lung cancer. Our study dissects out the mechanism of action of h-Prune in tumorigenic cells and also sheds light on the identification of a new therapeutic target in non-small-cell lung cancer.