Androgen receptor regulates eIF5A2 expression and promotes prostate cancer metastasis via EMT
Abstract Androgen receptor (AR) is an androgen-activated transcription factor of the nuclear receptor superfamily. AR plays a role in the development and progression of prostate cancer (PCa). However, the exact role of AR in PCa metastasis remains unclear. In the present study, we aimed to elucidate...
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| Autores principales: | , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Publishing Group
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/a773eed3739a4adeaa41a3199fdc901d |
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| Sumario: | Abstract Androgen receptor (AR) is an androgen-activated transcription factor of the nuclear receptor superfamily. AR plays a role in the development and progression of prostate cancer (PCa). However, the exact role of AR in PCa metastasis remains unclear. In the present study, we aimed to elucidate the function of AR in PCa. We found that eukaryotic translation initiation factor (EIF) 5A2, an elongation factor that induces epithelial-to-mesenchymal transition (EMT) in PCa cells, was significantly upregulated after 5α-dihydrotestosterone (DHT) stimulation and downregulated after anti‐androgen bicalutamide treatment in PCa cells with high AR expression, but not in cells with low AR expression. Moreover, eIF5A2 knockdown could eliminate DHT-induced invasion and migration of AR-positive PCa cells. DHT treatment decreased epithelial expression of E‐cadherin and β-catenin but increased the expression of the mesenchymal marker proteins Vimentin and N-cadherin. DHT therefore induced EMT, and knockdown of eIF5A2 inhibited DHT-induced EMT. Moreover, in vivo study, Luciferase signals from the lungs of the eIF5A2 plasmid group indicated higher metastasis ability, and the eIF5A2 siRNA group had lower metastasis ability. Our results suggest that AR positively regulates eIF5A2 expression in androgen-dependent cells, and stimulation of AR expression and signaling in prostate tumors promotes PCa metastasis by EMT induction and upregulation of eIF5A2. |
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