Facilitates chromatin transcription complex is an "accelerator" of tumor transformation and potential marker and target of aggressive cancers

Cell Rep. 2013 Jul 11;4(1):159-73. doi: 10.1016/j.celrep.2013.06.013. Epub 2013 Jul 3.

Abstract

The facilitates chromatin transcription (FACT) complex is involved in chromatin remodeling during transcription, replication, and DNA repair. FACT was previously considered to be ubiquitously expressed and not associated with any disease. However, we discovered that FACT is the target of a class of anticancer compounds and is not expressed in normal cells of adult mammalian tissues, except for undifferentiated and stem-like cells. Here, we show that FACT expression is strongly associated with poorly differentiated aggressive cancers with low overall survival. In addition, FACT was found to be upregulated during in vitro transformation and to be necessary, but not sufficient, for driving transformation. FACT also promoted survival and growth of established tumor cells. Genome-wide mapping of chromatin-bound FACT indicated that FACT's role in cancer most likely involves selective chromatin remodeling of genes that stimulate proliferation, inhibit cell death and differentiation, and regulate cellular stress responses.

Publication types

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

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Differentiation
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism*
  • Chromatin / genetics
  • Chromatin / metabolism*
  • Chromatin Assembly and Disassembly*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Neoplastic*
  • Genome, Human
  • High Mobility Group Proteins / genetics
  • High Mobility Group Proteins / metabolism*
  • Humans
  • MCF-7 Cells
  • Mice
  • Mice, Inbred C57BL
  • Mice, SCID
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Transcriptional Elongation Factors / genetics
  • Transcriptional Elongation Factors / metabolism*

Substances

  • Cell Cycle Proteins
  • Chromatin
  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • SSRP1 protein, human
  • SUPT16H protein, human
  • Supt16 protein, mouse
  • Transcription Factors
  • Transcriptional Elongation Factors
  • Ssrp1 protein, mouse

Associated data

  • GEO/GSE45393