ELF3 is an antagonist of oncogenic-signalling-induced expression of EMT-TF ZEB1

Cancer Biol Ther. 2019;20(1):90-100. doi: 10.1080/15384047.2018.1507256. Epub 2018 Aug 27.


Background: Epithelial-to-mesenchymal transition (EMT) is a key step in the transformation of epithelial cells into migratory and invasive tumour cells. Intricate positive and negative regulatory processes regulate EMT. Many oncogenic signalling pathways can induce EMT, but the specific mechanisms of how this occurs, and how this process is controlled are not fully understood. Methods: RNA-Seq analysis, computational analysis of protein networks and large-scale cancer genomics datasets were used to identify ELF3 as a negative regulator of the expression of EMT markers. Western blotting coupled to siRNA as well as analysis of tumour/normal colorectal cancer panels was used to investigate the expression and function of ELF3. Results: RNA-Seq analysis of colorectal cancer cells expressing mutant and wild-type β-catenin and analysis of colorectal cancer cells expressing inducible mutant RAS showed that ELF3 expression is reduced in response to oncogenic signalling and antagonizes Wnt and RAS oncogenic signalling pathways. Analysis of gene-expression patterns across The Cancer Genome Atlas (TCGA) and protein localization in colorectal cancer tumour panels showed that ELF3 expression is anti-correlated with β-catenin and markers of EMT and correlates with better clinical prognosis. Conclusions: ELF3 is a negative regulator of the EMT transcription factor (EMT-TF) ZEB1 through its function as an antagonist of oncogenic signalling.

Keywords: Oncogenic signalling; RNA-seq; Wnt signalling; epithelial-mesenchymal transition; protein networks.

Publication types

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

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • DNA-Binding Proteins / metabolism*
  • Datasets as Topic
  • Epithelial-Mesenchymal Transition / genetics*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Prognosis
  • Proto-Oncogene Proteins c-ets / metabolism*
  • RNA-Seq
  • Survival Analysis
  • Tissue Array Analysis
  • Transcription Factors / metabolism*
  • Wnt Signaling Pathway / genetics
  • Zinc Finger E-box-Binding Homeobox 1 / genetics*
  • ras Proteins / metabolism


  • DNA-Binding Proteins
  • ELF3 protein, human
  • Proto-Oncogene Proteins c-ets
  • Transcription Factors
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1
  • ras Proteins