Please use this identifier to cite or link to this item: http://hdl.handle.net/1893/23223
Appears in Collections:Biological and Environmental Sciences Journal Articles
Peer Review Status: Refereed
Title: Targeting the SIN3A-PF1 interaction inhibits epithelial to mesenchymal transition and maintenance of a stem cell phenotype in triple negative breast cancer
Authors: Bansal, Nidhi
Petrie, Kevin
Christova, Rossitza
Chung, Chi-Yeh
Leibovitch, Boris
Howell, Louise
Gil, Veronica
Sbirkov, Yordan
Lee, EunJee
Wexler, Joanna
Ariztia, Edgardo V
Sharma, Rajal
Zhu, Jun
Bernstein, Emily
Zhou, Ming-Ming
Zelent, Arthur
Farias, Eduardo F
Waxman, Samuel
Contact Email: kevin.petrie@stir.ac.uk
Keywords: epigenetics
SIN3
PF1
triple negative breast cancer
cancer stem cells
Issue Date: Oct-2015
Publisher: Impact Journals
Citation: Bansal N, Petrie K, Christova R, Chung C, Leibovitch B, Howell L, Gil V, Sbirkov Y, Lee E, Wexler J, Ariztia EV, Sharma R, Zhu J, Bernstein E, Zhou M, Zelent A, Farias EF & Waxman S (2015) Targeting the SIN3A-PF1 interaction inhibits epithelial to mesenchymal transition and maintenance of a stem cell phenotype in triple negative breast cancer, Oncotarget, 6 (33), pp. 34087-34105.
Abstract: Triple negative breast cancer (TNBC) is characterized by a poorly differentiated phenotype and limited treatment options. Aberrant epigenetics in this subtype represent a potential therapeutic opportunity, but a better understanding of the mechanisms contributing to the TNBC pathogenesis is required. The SIN3 molecular scaffold performs a critical role in multiple cellular processes, including epigenetic regulation, and has been identified as a potential therapeutic target. Using a competitive peptide corresponding to the SIN3 interaction domain of MAD (Tat-SID), we investigated the functional consequences of selectively blocking the paired amphipathic α-helix (PAH2) domain of SIN3. Here, we report the identification of the SID-containing adaptor PF1 as a factor required for maintenance of the TNBC stem cell phenotype and epithelial-to-mesenchymal transition (EMT). Tat-SID peptide blocked the interaction between SIN3A and PF1, leading to epigenetic modulation and transcriptional downregulation of TNBC stem cell and EMT markers. Importantly, Tat-SID treatment also led to a reduction in primary tumor growth and disseminated metastatic diseasein vivo. In support of these findings, knockdown ofPF1expression phenocopied treatment with Tat-SID bothin vitroandin vivo. These results demonstrate a critical role for a complex containing SIN3A and PF1 in TNBC and provide a rational for its therapeutic targeting.
Type: Journal Article
URI: http://hdl.handle.net/1893/23223
DOI Link: http://dx.doi.org/10.18632/oncotarget.6048
Rights: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Affiliation: Mount Sinai School of Medicine
Biological and Environmental Sciences
Institute of Cancer Research
Mount Sinai School of Medicine
Mount Sinai School of Medicine
Institute of Cancer Research
Institute of Cancer Research
Institute of Cancer Research
Mount Sinai School of Medicine
Mount Sinai School of Medicine
Mount Sinai School of Medicine
Mount Sinai School of Medicine
Institute of Cancer Research
Mount Sinai School of Medicine
Mount Sinai School of Medicine
Institute of Cancer Research
Mount Sinai School of Medicine
Mount Sinai School of Medicine

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