H-Prune through GSK-3β interaction sustains canonical WNT/β-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, Jamie, Dale, Trevor Clive ORCID: https://orcid.org/0000-0002-4880-9963, Decraene, C., Chiappetta, G., Piantedosi, F., Calabrese, C. and Zollo, M. 2014. H-Prune through GSK-3β interaction sustains canonical WNT/β-catenin signaling enhancing cancer progression in NSCLC. Oncotarget 5 (14) , pp. 5736-5749. 10.18632/oncotarget.2169

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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-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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences European Cancer Stem Cell Research Institute (ECSCRI)
Uncontrolled Keywords:	h-Prune; lung cancer; diagnostic marker; WNT/β-catenin signalling; Gsk-3β; Wnt3a
Publisher:	Impact Journals
ISSN:	1949-2553
Date of First Compliant Deposit:	19 February 2019
Date of Acceptance:	4 July 2014
Last Modified:	04 Jul 2023 13:22
URI:	https://orca.cardiff.ac.uk/id/eprint/64227

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