MTDH/SND1 Protein Complex in ERG-Mediated Transformation and Therapeutic Resistance
Abstract
In this reporting period, I found the first time that ERG could interact with SND1/MTDH protein complex in prostate cancer cell. I also identified the functional domains responsible for binding between ERG and SND1/MTDH complex. Our RNA-Seq experiment found a highly statistically significant overlap between genes regulated by ERG and SND1/MTDH proteins in VCaP cells. ERG and SND1 act in a concert and SND1 is necessary for ERG-mediated activation of some of its gene targets. Furthermore, CUT and RUN assay results suggested that ERG and SND1 bind to the same DNA regulatory elements in FZD8 and HPN gene promoters. These results suggested that SND1/MTDH complex is involved in ERG-mediated transcriptional regulation. I found that SND1/MTDH were both necessary and sufficient for ERG-mediated transformation of RWPE-1 cells. In addition, ERG, SND1 and MTDH are required for prostate cancer cell proliferation and invasion, and overexpression of SND1 rescues the effects of ERG knockdown in VCaP cells. Our results suggested that SND1/MTDH complex is involved in ERG-mediated prostate cancer and it may be considered as a therapeutic target in ERG-positive prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2021
- Accession Number
- AD1133881
Entities
People
- Sheng-you Liao
Organizations
- Fred Hutchinson Cancer Center