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

被引：44

作者：

Carotenuto, Marianeve ^{[1
,2
]}

De Antonellis, Pasqualino ^{[1
,2
]}

Liguori, Lucia ^{[1
,2
]}

Benvenuto, Giovanna ^{[3
]}

Magliulo, Daniela ^{[1
,2
]}

Alonzi, Alessandro ^{[1
,2
]}

Turino, Cecilia ^{[4
]}

Attanasio, Carmela ^{[1
,2
]}

Damiani, Valentina ^{[1
,2
]}

Bello, Anna Maria ^{[1
,2
]}

Vitiello, Fabiana ^{[5
]}

Pasquinelli, Rosa ^{[6
]}

Terracciano, Luigi ^{[7
]}

Federico, Antonella ^{[8
]}

Fusco, Alfredo ^{[8
]}

Freeman, Jamie ^{[9
]}

Dale, Trevor C. ^{[9
]}

Decraene, Charles ^{[10
,11
]}

Chiappetta, Gennaro ^{[6
]}

Piantedosi, Francovito ^{[5
]}

Calabrese, Cecilia ^{[4
]}

Zollo, Massimo ^{[1
,2
,12
]}

机构：

[1] Ctr Ingn Genet & Biotecnol Avanzate CEINGE, Naples, Italy

[2] Univ Naples Federico II, Dipartimento Med Mol & Biotecnol Med, Naples, Italy

[3] Villa Comunale, Stn Zool Anthon Dohrn, Naples, Italy

[4] Clin Seconda Univ Napoli, Dipartimento Sci Cardiotorac & Resp, Naples, Italy

[5] AORN Vincenzo Monaldi, Day Hosp Pneumol & Pneumoncol, Dipartimento Pneumol & Tisiol, Naples, Italy

[6] Fdn G Pascale, Natl Canc Inst, Funct Genom Unit, Naples, Italy

[7] Univ Basel, Inst Pathol, Mol Pathol Div, CH-4003 Basel, Switzerland

[8] CNR, Ist Endocrinol & Oncol Sperimentale, Dipartimento Biol & Patol Cellulare & Mol, I-80125 Naples, Italy

[9] Cardiff Univ, Sch Biosci, Cardiff CF10 3AX, S Glam, Wales

[10] Inst Curie, Ctr Rech, Translat Res Dept, Paris, France

[11] CNRS, UMR144, Paris, France

[12] Azienda Osped Federico II, DAI Med Trasfus, Naples, Italy

来源：

ONCOTARGET | 2014年 / 5卷 / 14期

基金：

英国生物技术与生命科学研究理事会;

关键词：

h-Prune; lung cancer; diagnostic marker; WNT/beta-catenin signalling; Gsk-3; beta; Wnt3a; CELL LUNG-CANCER; GUIDELINES 2ND EDITION; BETA-CATENIN; BREAST-CANCER; WNT PATHWAY; EXPRESSION; SURVIVAL; OVEREXPRESSION; ADENOCARCINOMA; SEQUESTRATION;

D O I：

10.18632/oncotarget.2169

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 beta). Gsk-3 beta is a negative regulator of canonical WNT/beta-catenin signaling. Here, we investigate the role of Gsk-3 beta/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.

引用

页码：5736 / 5749

页数：14

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