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Spatial and Temporal Analysis of Active ERK in the C. elegans Germline
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ETS1 is a genome-wide effector of RAS/ERK signaling in epithelial cells

Joshua P Plotnik1, Justin A Budka2, Mary W Ferris2

  • 1Department of Biology, Indiana University, Bloomington, Indiana, USA.

Nucleic Acids Research
|October 9, 2014
PubMed

Insights

The RAS/ERK pathway drives cancer by altering gene expression. Our study reveals ETS1 transcription factor is crucial for RAS/ERK-driven cell migration and gene regulation in epithelial cancers.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genomics

Background:

  • The RAS/ERK pathway is frequently activated in carcinomas, promoting oncogenesis through transcriptional reprogramming.
  • The specific cis-regulatory elements and trans-acting factors mediating these RAS/ERK-induced transcriptional changes remain largely undefined.

Purpose of the Study:

  • To identify cis-regulatory elements and transcription factors involved in RAS/ERK-mediated transcriptional changes in epithelial cells.
  • To elucidate the role of ETS1 in RAS/ERK pathway-driven cell migration and gene expression.

Main Methods:

  • Genome-wide analysis to identify enriched transcription factor binding sites near cell migration genes.
  • In vivo screening of ETS proteins to determine their role in cell migration.
  • Genome-wide mapping of ETS protein occupancy and expression analysis.

Main Results:

  • A conserved ETS/AP-1 transcription factor binding site motif was enriched near RAS/ERK-activated cell migration genes.
  • ETS1 was identified as essential for RAS/ERK-activated cell migration, requiring ERK phosphorylation for its function.
  • ETS1 binds to enhancer ETS/AP-1 sequences and plays dual roles in activating migration genes and repressing negative feedback regulators of the RAS/ERK pathway.

Conclusions:

  • ETS1 is a key mediator of epithelial-specific RAS/ERK transcriptional functions, including cell migration and pathway activation.
  • ETS1's dual role in gene activation and repression is critical for robust RAS/ERK signaling in epithelial cancers.
  • Understanding ETS1's function provides insights into oncogenesis driven by the RAS/ERK pathway.

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