Repression of NR4A1 by a chromatin modifier promotes docetaxel resistance in PC-3 human prostate cancer cells.

Epigenetic silencing mechanisms play an important role in chemoresistance of human cancer. Here we report the upregulated expression of metastasis-associated protein 1 (MTA1), a component of the nucleosome remodeling deacetylation (NuRD) complex, in chemoresistant prostate cancer (PCa). MTA1 knockdown in PC-3 cells inhibited cell proliferation and enhanced docetaxel (DTX)-induced cell death. Conversely, overexpression of MTA1 promotes DTX chemoresistance in PC-3 cells. MTA1 acted as a potent corepressor of the nuclear receptor NR4A1 transcription by interacting with histone deacetylase 2 (HDAC2). These findings suggest that MTA1 may serve as a novel DTX-resistance promoter in PC-3 cells.