Downregulation of NDR1 contributes to metastasis of prostate cancer cells via activating epithelial-mesenchymal transition

Cancer Med. 2018 Jul;7(7):3200-3212. doi: 10.1002/cam4.1532. Epub 2018 May 7.

Abstract

The 5-year survival rate decreases rapidly once the prostate cancer has invaded distant organs, although patients with localized prostate cancer have a good prognosis. In recent years, increasing numbers of reports showed that circulating tumor cells (CTCs) may play an important role in tumor metastasis and they have stronger potential of invasion and migration compared with their parental cells. In our previous investigation, we isolated CTCs from prostate cancer cell lines PC3. In this study, we found a novel antimetastasis gene NDR1 by analyzing different gene expression between CTCs and PC3. Lower NDR1 gene and protein expression were found in both prostate cancer cell lines and clinical specimens. Besides, NDR1 function acting as metastasis inhibitor was discovered both in vitro and in vivo. Further, we also discovered that several epithelial-mesenchymal transition (EMT)-related genes were upregulated when decreased NDR1 in PC3 cell lines. Therefore, our results revealed a role of NDR1 in the suppression of prostate cancer cell metastasis and provided a potential mechanism of action, thus offering new therapeutic strategies against prostate cancer metastasis.

Keywords: NDR1; epithelial-mesenchymal transition; metastasis; prostate cancer.