H-Prune through GSK-3β interaction sustains canonical WNT/β-catenin signaling enhancing cancer progression in NSCLC.
H-Prune through GSK-3β interaction sustains canonical WNT/β-catenin signaling enhancing cancer progression in NSCLC.
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DOI：
10.18632/oncotarget.2169
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发表时间：
2014-07-30
期刊：
影响因子：
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通讯作者：
Zollo M
中科院分区：
文献类型：
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作者：
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;Piantedosi F;Calabrese C;Zollo M
H-Prune能将短链多聚磷酸盐(PPase活性)与cAMP-磷酸二酯酶(PDE)结合在一起，这是迄今为止通过其过度表达而影响不同人类癌症的最新基因。H-Prune与糖原合成酶-3(GSK-3)β协同促进细胞迁移。GSK-3β是典型的WnT/β-连环蛋白信号的负调控因子。在这里，我们研究了GSK-3β/h-Prune复合体在Wnt/β-连环蛋白信号调节中的作用，证明了h-Prune也有能力通过分泌Wnt3a以旁分泌的方式激活Wnt信号。体内研究表明，h-Prune沉默可以抑制肺转移的形成，提高小鼠的存活率。我们用ELISA法测定了肺癌患者外周血中h-Prune的水平，结果表明h-Prune是肺癌的早期诊断标志物。我们的研究揭示了h-Prune在致瘤细胞中的作用机制，也为寻找新的非小细胞肺癌治疗靶点提供了线索。
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.