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TRPS1 Is a Lineage-Specific Transcriptional Dependency in Breast Cancer.
- Source :
-
Cell reports [Cell Rep] 2018 Oct 30; Vol. 25 (5), pp. 1255-1267.e5. - Publication Year :
- 2018
-
Abstract
- Perturbed epigenomic programs play key roles in tumorigenesis, and chromatin modulators are candidate therapeutic targets in various human cancer types. To define singular and shared dependencies on DNA and histone modifiers and transcription factors in poorly differentiated adult and pediatric cancers, we conducted a targeted shRNA screen across 59 cell lines of 6 cancer types. Here, we describe the TRPS1 transcription factor as a strong breast cancer-specific hit, owing largely to lineage-restricted expression. Knockdown of TRPS1 resulted in perturbed mitosis, apoptosis, and reduced tumor growth. Integrated analysis of TRPS1 transcriptional targets, chromatin binding, and protein interactions revealed that TRPS1 is associated with the NuRD repressor complex. These findings uncover a transcriptional network that is essential for breast cancer cell survival and propagation.<br /> (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Cell Line, Tumor
Cell Survival genetics
Female
HEK293 Cells
Humans
Mi-2 Nucleosome Remodeling and Deacetylase Complex metabolism
Protein Binding
RNA, Small Interfering metabolism
Repressor Proteins metabolism
Triple Negative Breast Neoplasms metabolism
Triple Negative Breast Neoplasms pathology
Breast Neoplasms genetics
Breast Neoplasms pathology
Cell Lineage
DNA-Binding Proteins metabolism
Transcription Factors metabolism
Transcription, Genetic
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 25
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 30380416
- Full Text :
- https://doi.org/10.1016/j.celrep.2018.10.023