TRPS1 Is a Lineage-Specific Transcriptional Dependency in Breast Cancer

Cell Rep. 2018 Oct 30;25(5):1255-1267.e5. doi: 10.1016/j.celrep.2018.10.023.


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.

Keywords: Lineage dependency; NuRD complex; TRPS1; breast cancer; mitosis; shRNA screen; transcriptional repressor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Lineage*
  • Cell Survival / genetics
  • DNA-Binding Proteins / metabolism*
  • Female
  • HEK293 Cells
  • Humans
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex / metabolism
  • Protein Binding
  • RNA, Small Interfering / metabolism
  • Repressor Proteins / metabolism
  • Transcription Factors / metabolism*
  • Transcription, Genetic*
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology


  • DNA-Binding Proteins
  • RNA, Small Interfering
  • Repressor Proteins
  • TRPS1 protein, human
  • Transcription Factors
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex