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-3beta). Gsk-3beta is a negative regulator of canonical WNT/beta-catenin signaling. Here, we investigate the role of Gsk-3beta/h-Prune complex in the regulation of WNT/beta-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.
H-Prune through GSK-3?? interaction sustains canonical WNT/??-catenin signaling enhancing cancer progression in NSCLC / Carotenuto, M., De Antonellis, P., Liguori, L., Benvenuto, G., Magliulo, D., Alonzi, A., Turino, C., Attanasio, C., Damiani, V., Bello, A.m., Vitiello, F., Pasquinelli, R., Terracciano, L., Federico, A., Fusco, A., Freeman, J., Dale, T.c., Decraene, C., Chiappetta, G., Piantedosi, F., et al.. - In: ONCOTARGET. - ISSN 1949-2553. - 5:14(2014), pp. 5736-5749. [10.18632/oncotarget.2169]
H-Prune through GSK-3?? interaction sustains canonical WNT/??-catenin signaling enhancing cancer progression in NSCLC.
De Antonellis P;FUSCO, ALFREDO;ZOLLO, MASSIMO
2014
Abstract
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-3beta). Gsk-3beta is a negative regulator of canonical WNT/beta-catenin signaling. Here, we investigate the role of Gsk-3beta/h-Prune complex in the regulation of WNT/beta-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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
