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

Marianeve Carotenuto, Pasqualino D. De Antonellis, Lucia Liguori, Giovanna Benvenuto, Daniela Magliulo, Alessandro Alonzi, Cecilia Turino, Carmela Attanasio, Valentina Damiani, Anna Maria Bello, Fabiana Vitiello, Rosa Pasquinelli, Luigi Terracciano, Antonella Federico, Alfredo Fusco, Jamie Freeman, Trevor C. Dale, Charles Decraene, Gennaro Chiappetta, Francovito PiantedosiCecilia Calabrese, Massimo Zollo

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)5736-5749
Number of pages14
JournalOncotarget
Volume5
Issue number14
Publication statusPublished - 2014

Keywords

  • Diagnostic marker
  • Gsk-3β
  • h-Prune
  • Lung cancer
  • WNT/β-catenin signalling
  • Wnt3a

ASJC Scopus subject areas

  • Oncology
  • Medicine(all)

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  • Cite this

    Carotenuto, M., De Antonellis, P. D., 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., ... Zollo, M. (2014). H-Prune through GSK-3β interaction sustains canonical WNT/β-catenin signaling enhancing cancer progression in NSCLC. Oncotarget, 5(14), 5736-5749.