Bansai et al. in 2015 reported a novel therapeutic approach for blocking interactions of the SIN3 PAH2 domain in triple negative breast cancer. The researchers reported the identification of the SID-containing adaptor PF1 as a factor required for maintenance of the triple negative breast cancer (TNBC) stem cell phenotype and epithelial-to-mesenchymal transition (EMT). The research group employed a competitive peptide corresponding to the SIN3 interaction domain of MAD (Tat-SID: YGRKKRRQGGG-VRMNIQMLLEAADYLERRER) for the investigation of the functional consequences of selectively blocking the paired amphipathic α-helix (PAH2) domain of SIN3.
Sin3 contains four paired amphipathic helix (PAH) domains, PAH1, PAH2, PAH3 and PAH4. The Tat-SID peptide used blocked the interaction between SIN3A and PF1. This interaction resulted in epigenetic modulation and transcriptional downregulation of TNBC stem cell and EMT markers.
Nidhi Bansal, Kevin Petrie, Rossitza Christova, Chi-Yeh Chung, Boris A. Leibovitch, Louise Howell, Veronica Gil, Yordan Sbirkov, EunJee Lee, Joanna Wexler, Edgardo V. Ariztia, Rajal Sharma, Jun Zhu, Emily Bernstein, MingMing Zhou, Arthur Zelent, Eduardo Farias and Samuel Waxman; Targeting the SIN3A-PF1 interaction inhibits epithelial to mesenchymal transition and maintenance of a stem cell phenotype in triple negative breast cancer.