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Related Experiment Video

Updated: May 12, 2025

High-throughput Screening for Chemical Modulators of Post-transcriptionally Regulated Genes
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Development and validation of a high-throughput screening pipeline of compound libraries to target EMT.

Sven Jonckheere1,2,3, Joachim Taminau1,2,3, Jamie Adams4

  • 1Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium.

Cell Death and Differentiation
|May 9, 2025
PubMed

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Summary
This summary is machine-generated.

Epithelial to Mesenchymal transition (EMT) drives cancer's spread. Researchers developed a high-throughput screening assay to find drugs blocking EMT, identifying RepSox as a potent inhibitor in breast and colorectal cancer models.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Epithelial to Mesenchymal transition (EMT) is crucial for cell plasticity, invasiveness, migration, and stemness.
  • EMT is orchestrated by transcription factors and plays a role in malignant progression of cancers like breast and colorectal cancer (CRC).
  • Targeting EMT is a promising strategy for novel cancer therapeutics.

Purpose of the Study:

  • To develop a high-throughput screening assay for identifying small molecules that interfere with EMT.
  • To validate identified anti-EMT compounds in preclinical cancer models.

Main Methods:

  • Development of a phenotypic dual EMT Sensor screening assay for high-throughput screening.
  • Proof-of-concept screening to identify anti-EMT repurposing drugs.

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  • In vitro validation of drug efficacy in breast and colorectal cancer cell lines.
  • In vivo validation using a Drosophila melanogaster metastatic CRC model.

    • Main Results:

    • A novel phenotypic dual EMT Sensor screening assay was successfully developed.
    • The screening identified several anti-EMT repurposing drugs.
    • RepSox, a TGF-β type I receptor ALK5 inhibitor, potently blocked EMT in vitro.
    • Identified anti-EMT compounds suppressed metastatic behavior in vivo in a Drosophila CRC model.

    Conclusions:

    • The developed EMT Sensor assay is effective for high-throughput screening of anti-EMT compounds.
    • RepSox demonstrates potent anti-EMT activity in vitro and suppresses metastasis in vivo.
    • This study validates EMT as a therapeutic target and identifies potential drugs for cancer treatment.