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Suppression Of β-catenin Nuclear Translocation By CGP57380 Decelerates Poor Progression And Potentiates Radiation-Induced Apoptosis in Nasopharyngeal Carcinoma

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-cate...

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Autores principales: Wang, Weiyuan, Wen, Qiuyuan, Luo, Jiadi, Chu, Shuzhou, Chen, Lingjiao, Xu, Lina, Zang, Hongjing, Alnemah, Mohannad Ma, Li, Jinghe, Zhou, Jianhua, Fan, Songqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5485425/
https://www.ncbi.nlm.nih.gov/pubmed/28656063
http://dx.doi.org/10.7150/thno.17665
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author Wang, Weiyuan
Wen, Qiuyuan
Luo, Jiadi
Chu, Shuzhou
Chen, Lingjiao
Xu, Lina
Zang, Hongjing
Alnemah, Mohannad Ma
Li, Jinghe
Zhou, Jianhua
Fan, Songqing
author_facet Wang, Weiyuan
Wen, Qiuyuan
Luo, Jiadi
Chu, Shuzhou
Chen, Lingjiao
Xu, Lina
Zang, Hongjing
Alnemah, Mohannad Ma
Li, Jinghe
Zhou, Jianhua
Fan, Songqing
author_sort Wang, Weiyuan
collection PubMed
description 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.
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spelling pubmed-54854252017-06-27 Suppression Of β-catenin Nuclear Translocation By CGP57380 Decelerates Poor Progression And Potentiates Radiation-Induced Apoptosis in Nasopharyngeal Carcinoma Wang, Weiyuan Wen, Qiuyuan Luo, Jiadi Chu, Shuzhou Chen, Lingjiao Xu, Lina Zang, Hongjing Alnemah, Mohannad Ma Li, Jinghe Zhou, Jianhua Fan, Songqing Theranostics Research Paper 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. Ivyspring International Publisher 2017-05-30 /pmc/articles/PMC5485425/ /pubmed/28656063 http://dx.doi.org/10.7150/thno.17665 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Wang, Weiyuan
Wen, Qiuyuan
Luo, Jiadi
Chu, Shuzhou
Chen, Lingjiao
Xu, Lina
Zang, Hongjing
Alnemah, Mohannad Ma
Li, Jinghe
Zhou, Jianhua
Fan, Songqing
Suppression Of β-catenin Nuclear Translocation By CGP57380 Decelerates Poor Progression And Potentiates Radiation-Induced Apoptosis in Nasopharyngeal Carcinoma
title Suppression Of β-catenin Nuclear Translocation By CGP57380 Decelerates Poor Progression And Potentiates Radiation-Induced Apoptosis in Nasopharyngeal Carcinoma
title_full Suppression Of β-catenin Nuclear Translocation By CGP57380 Decelerates Poor Progression And Potentiates Radiation-Induced Apoptosis in Nasopharyngeal Carcinoma
title_fullStr Suppression Of β-catenin Nuclear Translocation By CGP57380 Decelerates Poor Progression And Potentiates Radiation-Induced Apoptosis in Nasopharyngeal Carcinoma
title_full_unstemmed Suppression Of β-catenin Nuclear Translocation By CGP57380 Decelerates Poor Progression And Potentiates Radiation-Induced Apoptosis in Nasopharyngeal Carcinoma
title_short Suppression Of β-catenin Nuclear Translocation By CGP57380 Decelerates Poor Progression And Potentiates Radiation-Induced Apoptosis in Nasopharyngeal Carcinoma
title_sort suppression of β-catenin nuclear translocation by cgp57380 decelerates poor progression and potentiates radiation-induced apoptosis in nasopharyngeal carcinoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5485425/
https://www.ncbi.nlm.nih.gov/pubmed/28656063
http://dx.doi.org/10.7150/thno.17665
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