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

Author

Carotenuto M, De Antonellis P, Liguori L, Benvenuto G, Magliulo D, Alonzi A, Turino C, Attanasio C, Damiani V, Am, Bello, Vitiello F, Pasquinelli R, Terracciano L, Federico A, Fusco A, Freeman J, Trevor Dale, Decraene C, Chiappetta G, Piantedosi F, Carotenuto, M, De Antonellis, P, Liguori, L, Benvenuto, G, Magliulo, D, Alonzi, A, Turino, C, Attanasio, C, Damiani, V, Bello, Am, Vitiello, F, Pasquinelli, R, Terracciano, L, Federico, A, Fusco, A, Freeman, J, Dale, Tc, Decraene, C, Chiappetta, G, and Zollo, M

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

Author

Trevor Clive Dale, Giovanna Benvenuto, Francovito Piantedosi, Marianeve Carotenuto, Carmela Attanasio, Fabiana Vitiello, Cecilia Calabrese, Luigi Terracciano, Rosa Pasquinelli, Massimo Zollo, Lucia Liguori, Charles Decraene, Jamie Freeman, Valentina Damiani, Pasqualino De Antonellis, Antonella Federico, Daniela Magliulo, Anna Maria Bello, Cecilia Turino, Alfredo Fusco, Gennaro Chiappetta, Alessandro Alonzi, Carotenuto, M, De Antonellis, P, Liguori, L, Benvenuto, G, Magliulo, D, Alonzi, A, Turino, C, Attanasio, C, Damiani, V, Bello, Am, Vitiello, F, Pasquinelli, R, Terracciano, L, Federico, A, Fusco, Alfredo, Freeman, J, Dale, Tc, Decraene, C, Chiappetta, G, Piantedosi, F, Calabrese, C, Zollo, Massimo, Fusco, A, Calabrese, Cecilia, and Zollo, M.

Subjects
Lung Neoplasms, Beta-catenin, Mice, Nude, Glycogen Synthase Kinase 3, Mice, Paracrine signalling, WNT/β-catenin signalling, Gsk-3β, GSK-3, Carcinoma, Non-Small-Cell Lung, medicine, Animals, Humans, Wnt Signaling Pathway, GSK3B, beta Catenin, Glycogen Synthase Kinase 3 beta, biology, diagnostic marker, fungi, Wnt signaling pathway, Cancer, LRP6, Wnt3a, LRP5, medicine.disease, Phosphoric Monoester Hydrolases, 3. Good health, lung cancer, Oncology, nervous system, Disease Progression, Cancer research, biology.protein, Heterografts, Female, Carrier Proteins, h-Prune, Research Paper
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.

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