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

Authors :
Tianying Chen
Wangyue Jia
Bo Zhang
Hanqi Xie
Qiong Wu
Source :
Synthetic and Systems Biotechnology, Vol 9, Iss 1, Pp 1-10 (2024)
Publication Year :
2024
Publisher :
KeAi Communications Co., Ltd., 2024.

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.

Details

Language :
English
ISSN :
2405805X
Volume :
9
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Synthetic and Systems Biotechnology
Publication Type :
Academic Journal
Accession number :
edsdoj.81f8745128b64d299a48a602fc33177b
Document Type :
article
Full Text :
https://doi.org/10.1016/j.synbio.2023.11.010