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Updated: Jul 6, 2025

Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
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.
Abstract:
The epithelial mesenchymal transition (EMT) plays significant roles in the progression of cancer and fibrotic disease. Moreover, this process is reversible, resulting in mesenchymal epithelial transition (MET), which plays an important role in cancer metastasis. There is a lack of methods to trace and target EMT cells using synthetic biology circuits, which makes it difficult to study the cell fate or develop targeted treatments. In this study, we introduced responsive EMT sensing circuits, which sense the EMT using specific promoters that respond to transcription factors typical of EMT activation (EMT-TFs). The transcriptional strength of EMT-sensing promoters decreased more than 13-fold in response to the overexpression of the EMT-TF. Then, the NOT gate circuits were built by placing the tetR transcription repressor under the control of EMT sensing promoters and expressed an output signal using the constitutive CMV promoter modified with tetO sites This circuit is named EMT sensing and responding circuits .When the EMT transcription factors was present, we observed a 5.8-fold signal increase in the system. Then, we successfully distinguished mesenchymal breast cancer cells from epithelial cancer cells and repressed the proliferation of EMT tumor cells using our circuits. The EMT sensing and responding circuits are promising tools for the identification of EMT cells, which is crucial for EMT-related disease therapy and investigating the mechanisms underlying the reversible EMT process.
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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