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

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-3?). Gsk-3? is a negative regulator of canonical WNT/?-catenin signaling. Here, we investigate the role of Gsk-3?/h-Prune complex in the regulation of WNT/?-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.

SUBMITTER: Carotenuto M 

PROVIDER: S-EPMC4170634 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature