Nucleoporin 153 regulates estrogen-dependent nuclear translocation of endothelial nitric oxide synthase and estrogen receptor beta in prostate cancer.

Simona Nanni, Claudio Grassi, Alfredo Pontecorvi, Lorenza Bacci, Antonella Farsetti, Agnese Re, Claudia Colussi

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7 Citazioni (Scopus)

Abstract

Nucleoporin 153 (Nup153), key regulator of nuclear import/export, has been recently associated to oncogenic properties in pancreatic and breast tumour cells modulating either cell motility and migration or gene expression by chromatin association. In the present work, we have characterized the role of Nup153 in a cellular model of prostate cancer (PCa). The analysis of several immortalized cell lines derived from freshly explants of prostate cancer specimens showed that Nup153 protein was higher and present in multimeric complexes with eNOS and ERß as compared to normal/hyperplastic prostate epithelial cells. This phenomenon was enhanced in the presence of 17ß-estradiol (E2, 10-7M). Further experiments revealed that eNOS and ERß were present in a DNA binding complexes associated with Nup153 promoter as demonstrated by ChIPs. Notably, after Nup153 depletion (siNup153), a reduction of migration capacity and colony formation in primary tumor-derived and metastatic PCa cells was observed. In addition, eNOS and ERß nuclear localization was lost upon siNup153 regardless of E2 treatment, suggesting that Nup153 is a key regulator of prostate cancer cell function and of the nuclear translocation of these proteins in response to hormone stimulus. Taken altogether our findings indicate that in PCa cells: i. the expression and function of Nup153 is modulated by estrogen signaling; ii. Nup153 contributes to cell migration and proliferation; iii. Nup153 regulates the nuclear translocation of eNOS and ERß by forming a multimeric complex. Our findings unveil Nup153 as a novel component of the estrogen-dependent multimeric complex, thus representing a potential therapeutic candidate in prostate cancer.
Lingua originaleEnglish
pagine (da-a)27985-27997
Numero di pagine13
RivistaOncotarget
Volume9
DOI
Stato di pubblicazionePubblicato - 2018

Keywords

  • ENOS
  • Estrogen Receptor signaling
  • Molecular biomarkers
  • Nucleoporin 153
  • Prostate cancer

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