Updated project metadata. ERG is a transcriptional factor, which is recombined with promoter of TMPRSS2 and prominently overexpressed in half of human prostate cancers. The mechanisms of ERG-mediated oncogenesis are not completely understood. We performed an unbiased Mass Spectrometry screen for ERG-binding proteins and found that ERG binds to MTDH/SND1 protein complex in prostate cancer cells. We determined that ERG binds to the SND1/MTDH protein complex via SND1 and this interaction plays a critical role in ERG-mediated cancer.