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Targeting the SIN3A-PF1 interaction inhibits epithelial to mesenchymal transition and maintenance of a stem cell phenotype in triple negative breast cancer.

Bansal, Nidhi, Petrie, Kevin, Christova, Rossitza, Chung, Chi-Yeh, Leibovitch, Boris A, 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 and Waxman, Samuel (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. 34087-105. ISSN 1949-2553

Item Type: Article

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 disease in vivo. In support of these findings, knockdown of PF1 expression phenocopied treatment with Tat-SID both in vitro and in vivo. These results demonstrate a critical role for a complex containing SIN3A and PF1 in TNBC and provide a rational for its therapeutic targeting.

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More Information

Depositing User: Kevin Petrie

Identifiers

Item ID: 12442
Identification Number: https://doi.org/10.18632/oncotarget.6048
ISSN: 1949-2553
URI: http://sure.sunderland.ac.uk/id/eprint/12442
Official URL: https://www.oncotarget.com/article/6048/text/

Users with ORCIDS

ORCID for Kevin Petrie: ORCID iD orcid.org/0000-0002-9805-9152

Catalogue record

Date Deposited: 18 Aug 2020 19:04
Last Modified: 30 Sep 2020 10:48

Contributors

Author: Kevin Petrie ORCID iD
Author: Nidhi Bansal
Author: Rossitza Christova
Author: Chi-Yeh Chung
Author: Boris A Leibovitch
Author: Louise Howell
Author: Veronica Gil
Author: Yordan Sbirkov
Author: EunJee Lee
Author: Joanna Wexler
Author: Edgardo V Ariztia
Author: Rajal Sharma
Author: Jun Zhu
Author: Emily Bernstein
Author: Ming-Ming Zhou
Author: Arthur Zelent
Author: Eduardo Farias
Author: Samuel Waxman

University Divisions

Faculty of Health Sciences and Wellbeing > School of Medicine

Subjects

Sciences > Biomedical Sciences
Sciences > Health Sciences

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