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TRPS1 Is a Lineage-Specific Transcriptional Dependency in Breast Cancer.

Authors :
Witwicki RM
Ekram MB
Qiu X
Janiszewska M
Shu S
Kwon M
Trinh A
Frias E
Ramadan N
Hoffman G
Yu K
Xie Y
McAllister G
McDonald R
Golji J
Schlabach M
deWeck A
Keen N
Chan HM
Ruddy D
Rejtar T
Sovath S
Silver S
Sellers WR
Jagani Z
Hogarty MD
Roberts C
Brown M
Stegmaier K
Long H
Shivdasani RA
Pellman D
Polyak K
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.)

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