14-3-3 proteins modulate the ETS transcription factor ETV1 in prostate cancer.

ABSTRACT: Overexpression of the ETS-related transcription factor ETV1 can initiate neoplastic transformation of the prostate. ETV1 activity is highly regulated by phosphorylation, but the underlying mechanisms are unknown. Here we report that all 14-3-3 proteins, with the exception of the tumor suppressor 14-3-3?, can bind to ETV1 in a condition manner dictated by its prominent phosphorylation site S216. Non-? 14-3-3 proteins synergized with ETV1 to activate transcription of its target genes MMP-1 and MMP-7, which regulate extracellular matrix in the prostate tumor microenvironment. S216 mutation or 14-3-3? downregulation was sufficient to reduce ETV1 protein levels in prostate cancer cells, indicating that non-? 14-3-3 proteins protect ETV1 from degradation. Notably, S216 mutation also decreased ETV1-dependent migration and invasion in benign prostate cells. Downregulation of 14-3-3? reduced prostate cancer cell invasion and growth in the same manner as ETV1 attenuation. Finally, we showed that 14-3-3? and 14-3-3? were overexpressed in human prostate tumors. Taken together, our results showed that non-? 14-3-3 proteins are important modulators of ETV1 function that promote prostate tumorigenesis.

SUBMITTER: Oh S 

PROVIDER: S-EPMC3745528 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature