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Amlexanox targets the IKK-ɛ/TBK1/NF-κB signaling axis to suppress the epithelial-to-mesenchymal transition and prostate cancer metastasis

ABSTRACT: Tumor metastasis is the major cause of death for prostate cancer (PCa) patients. However, the treatment options for metastatic PCa are very limited. Epithelial-mesenchymal transition (EMT) has been reported to be an indispensable step for tumor metastasis and is suggested to associate with acquisition of cancer stem cell (CSC) attributes. Herein we establish a EMT reporter system based on firefly or renilla luciferase reporter driven by promoters of CDH1 and VIM genes. High-throughput drug screening from an approved drug library identifies Amlexanox, a commonly used drug to treat aphthous ulcers, to be a strong EMT inhibitor. Amlexanox significantly suppresses PCa cell migration, metastasis and tumor initiation capacity. Mechanistically, the inhibitory effect of Amlexanox on EMT and cell mobility is acted through targeting the IKK-ɛ/ TBK1/ NF-κB signaling pathway. Considering the known safety as well as the pharmacokinetic and pharmacodynamic profile of Amlexanox, our findings suggest a great potential of repositioning Amlexanox as a new anti-metastatic drug for PCa.

ORGANISM(S): Homo sapiens

PROVIDER: GSE110206 | GEO | 2018/07/20

REPOSITORIES: GEO

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