Suppression Of beta-catenin Nuclear Translocation By CGP57380 Decelerates Poor Progression And Potentiates Radiation-Induced Apoptosis in Nasopharyngeal Carcinoma
Suppression Of beta-catenin Nuclear Translocation By CGP57380 Decelerates Poor Progression And Potentiates Radiation-Induced Apoptosis in Nasopharyngeal Carcinoma
复制标题
CGP57380 抑制 β-连环蛋白核易位可减缓鼻咽癌的不良进展并增强放射诱导的细胞凋亡
作者：
Wang WY;Wen QY;Luo JD;Chu SZ;Chen LJ;Xu LN;Zang HJ;Alnemah MM;Li JH;Zhou JH;Fan SQ
Nuclear localization of β-catenin is essential for the progression of various human cancers via.transcriptional upregulation of downstream genes. The MAP kinase interacting serine/threonine.kinase (MNK)-eukaryotic translation initiation factor 4E (eIF4E) axis has been reported to activate.Wnt/β-catenin signaling, and CGP57380, an inhibitor of MNK kinases, inhibits the proliferation of.multiple cancers. In this study, we showed that β-catenin signaling (including β-catenin, cyclin D1,.c-Myc, and MMP-7) and p-eIF4E expression were elevated in nasopharyngeal carcinoma (NPC).compared with non-cancerous nasopharyngeal epithelial tissues, and was associated with clinical.characteristics of NPC patients. Lymph node metastasis, gender, aberrant β-catenin expression,.and elevated levels of MMP-7 and cyclin D1 were independent prognostic factors. Significantly,.expression of p-eIF4E was positively correlated with β-catenin, and targeting the MNK–eIF4E axis.with CGP57380 downregulated β-catenin in the nucleus, which in turn decreased proliferation,.cell cycle progression, migration, invasion, and metastasis of NPC in vitro and in vivo. CGP57380.also potentiated radiation-induced apoptosis in NPC. Moreover, CGP57380 upregulated β-catenin.in the cytoplasm thus blocking epithelial-mesenchymal transition (EMT), a key mechanism in cancer.cell invasiveness and metastasis. Mechanistically, inhibition of β-catenin nuclear translocation by.CGP57380 was dependent on AKT activation. Notably, identification of the MNK/eIF4E/β-catenin.axis might provide a potential target for overcoming the poor prognosis mediated by β-catenin in.NPC.
