title: H-Prune through GSK-3β interaction sustains canonical WNT/β-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-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.
authors.affiliation: Centro di Ingegneria Genetica e Biotecnologie Avanzate (CEINGE), Naples, Italy; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università 'Federico II' di Naples, Italy.
authors.forename: Marianeve
authors.initials: M
authors.lastname: Carotenuto
authors.affiliation: Centro di Ingegneria Genetica e Biotecnologie Avanzate (CEINGE), Naples, Italy; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università 'Federico II' di Naples, Italy.
authors.forename: Pasqualino
authors.initials: P
authors.lastname: De Antonellis
authors.affiliation: Centro di Ingegneria Genetica e Biotecnologie Avanzate (CEINGE), Naples, Italy; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università 'Federico II' di Naples, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Liguori
authors.affiliation: Stazione Zoologica Anthon Dohrn, Villa Comunale, Naples, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Benvenuto
authors.affiliation: Centro di Ingegneria Genetica e Biotecnologie Avanzate (CEINGE), Naples, Italy; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università 'Federico II' di Naples, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Magliulo
authors.affiliation: Centro di Ingegneria Genetica e Biotecnologie Avanzate (CEINGE), Naples, Italy; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università 'Federico II' di Naples, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Alonzi
authors.affiliation: Dipartimento di Scienze Cardiotoraciche e Respiratorie, Clinica Seconda Università degli Studi di Napoli, Naples, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Turino
authors.affiliation: Centro di Ingegneria Genetica e Biotecnologie Avanzate (CEINGE), Naples, Italy; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università 'Federico II' di Naples, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Attanasio
authors.affiliation: Centro di Ingegneria Genetica e Biotecnologie Avanzate (CEINGE), Naples, Italy; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università 'Federico II' di Naples, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Damiani
authors.affiliation: Centro di Ingegneria Genetica e Biotecnologie Avanzate (CEINGE), Naples, Italy; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università 'Federico II' di Naples, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Bello
authors.affiliation: Dipartimento di Pneumologia e Tisiologia, Day Hospital Pneumologia e Pneumoncologico, AORN Vincenzo Monaldi, Naples, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Vitiello
authors.affiliation: Functional Genomic Unit, National Cancer Institute, Fondazione G. Pascale, Naples, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Pasquinelli
authors.affiliation: Institute of Pathology, Molecular Pathology Division, University of Basel, Switzerland.
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
authors.affiliation: Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto Di Endocrinologia e Oncologia Sperimentale del CNR, Naples, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Federico
authors.affiliation: Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto Di Endocrinologia e Oncologia Sperimentale del CNR, Naples, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Fusco
authors.affiliation: School of Biosciences, Cardiff University, Museum Avenue, Cardiff, Wales, UK.
authors.forename: Jamie
authors.initials: J
authors.lastname: Freeman
authors.affiliation: School of Biosciences, Cardiff University, Museum Avenue, Cardiff, Wales, UK.
authors.forename: Trevor C
authors.initials: TC
authors.lastname: Dale
authors.affiliation: Translational Research Dept, Institut Curie, Centre de recherche, Paris, France; CNRS, UMR144, Paris, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Decraene
authors.affiliation: Functional Genomic Unit, National Cancer Institute, Fondazione G. Pascale, Naples, Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Chiappetta
authors.affiliation: Dipartimento di Pneumologia e Tisiologia, Day Hospital Pneumologia e Pneumoncologico, AORN Vincenzo Monaldi, Naples, Italy.
authors.forename: Francovito
authors.initials: F
authors.lastname: Piantedosi
authors.affiliation: Dipartimento di Scienze Cardiotoraciche e Respiratorie, Clinica Seconda Università degli Studi di Napoli, Naples, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Calabrese
authors.affiliation: Centro di Ingegneria Genetica e Biotecnologie Avanzate (CEINGE), Naples, Italy; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università 'Federico II' di Naples, Italy; Azienda Ospedaliera Federico II, DAI Medicina Trasfusionale Virologia, Naples, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Zollo
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000097:blood* / Q000235:genetics; D018450:Disease Progression; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D010744:Phosphoric Monoester Hydrolases; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C495270:CTNNB1 protein, human; D002352:Carrier Proteins; D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; C438732:PRUNE1 protein, human; D010744:Phosphoric Monoester Hydrolases