The absence of a biomarker to predict the aggressiveness of prostate cancer patients is the major obstacle in deciding which prostate cancer patient should be treated. In this report, we show that COUP transcription factor II (COUP-TFII), a member of the nuclear receptor superfamily, antagonizes the transforming growth factor (TGF)-β-induced growth barrier to facilitate tumor metastasis and provide a molecular mechanism for how PTEN indolent tumors acquire metastatic potential. More importantly, we identify that COUP-TFII expression or its signature serves as a predictor to stratify risk of biochemical recurrence in patients. Collectively, our findings identify a prognostic marker and therapeutic target for metastatic prostate cancer.

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