Development of peptidomimetic inhibitors of the ERG gene fusion product in prostate cancer (expression)

ABSTRACT: Transcription factors play a key role in the development of diverse cancers, and therapeutically targeting them has remained a challenge. In prostate cancer, the gene encoding the transcription factor ERG is recurrently rearranged and plays a critical role in prostate oncogenesis. Here, we identified a series of peptides that interact specifically with the DNA binding domain of ERG. The most prevalent consensus peptide series matched the tumor suppressor Deleted in Liver Cancer 1 (DLC1). ERG inhibitory peptides and derived peptidomimetics (EIPs) bound with high affinity and specificity leading to proteolytic degradation of ERG. The EIPs attenuated ERG-mediated transcription, chromatin recruitment, protein-protein interactions, cell invasion, and tumor growth. Thus, peptidomimetic targeting of transcription factor fusion products may provide a promising therapeutic strategy for prostate cancer as well as other cancers.

ORGANISM(S): Homo sapiens

PROVIDER: GSE58940 | GEO | 2014/07/15

SECONDARY ACCESSION(S): PRJNA254032

REPOSITORIES: GEO