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

Nucleoporin 153 regulates estrogen-dependent nuclear translocation of endothelial nitric oxide synthase and estrogen receptor beta in prostate cancer. Oncotarget. 2018 Jun 15;9(46):27985-27997 Authors: Re A, Colussi C, Nanni S, Aiello A, Bacci L, Grassi C, Pontecorvi A, Farsetti A 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 ERβ as compared to normal/hyperplastic prostate epithelial cells. This phenomenon was enhanced in the presence of 17β-estradiol (E2, 10-7M). Further experiments revealed that eNOS and ERβ 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 ERβ nuclear localization was lost upon siNup 153 regardless of E2 treatment, suggesting that Nup153 is a key regulator of prostate cancer ce...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research