EMT transcription factors activated circuits: A novel tool to study EMT dynamics and its therapeutic implications

Tianying Chen1, Wangyue Jia1, Bo Zhang1

  • 1MOE Key Laboratory of Bioinformatics, Center for Synthetic and System Biology, School of Life Sciences, Tsinghua University, Beijing, 100084, China.

Insights

Synthetic biology circuits can now identify and target cancer cells undergoing epithelial mesenchymal transition (EMT). These novel EMT sensing and responding circuits offer new avenues for cancer therapy and research into EMT-related diseases.

Area of Science:

  • Biotechnology
  • Synthetic Biology
  • Cancer Research

Background:

  • Epithelial mesenchymal transition (EMT) is crucial in cancer progression and fibrosis.
  • The reversible nature of EMT, known as mesenchymal epithelial transition (MET), is key to cancer metastasis.
  • Current methods for tracing and targeting EMT cells are limited, hindering research and treatment development.

Purpose of the Study:

  • To develop novel synthetic biology circuits for sensing and responding to EMT.
  • To enable the identification and potential targeting of EMT cells.
  • To facilitate the study of cell fate and targeted therapies in EMT-related diseases.

Main Methods:

  • Engineered EMT sensing circuits utilizing promoters responsive to EMT transcription factors (EMT-TFs).
  • Constructed NOT gate circuits incorporating EMT-sensing promoters and a tetR repressor.
  • Validated circuit performance through signal detection and cell proliferation assays.

Main Results:

  • EMT-sensing promoters showed a >13-fold decrease in transcriptional strength upon EMT-TF overexpression.
  • The developed EMT sensing and responding circuits exhibited a 5.8-fold signal increase in the presence of EMT transcription factors.
  • Successfully differentiated mesenchymal breast cancer cells from epithelial cancer cells and inhibited EMT tumor cell proliferation.

Conclusions:

  • The developed EMT sensing and responding circuits are effective tools for identifying EMT cells.
  • These circuits hold promise for advancing therapies for EMT-related diseases.
  • The circuits provide a valuable platform for investigating the mechanisms of reversible EMT.

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