Development and validation of a high-throughput screening pipeline of compound libraries to target EMT
- Author
- Sven Jonckheere, Joachim Taminau (UGent) , Jamie Adams, Jef Haerinck (UGent) , Jordy De Coninck (UGent) , Jeroen Verstappe (UGent) , Kato De Clercq (UGent) , Evelien Peeters (UGent) , Alexander Gheldof (UGent) , Eva De Smedt (UGent) , Vera Goossens (UGent) , Dominique Audenaert (UGent) , Aurelie Candi, Matthias Versele, Dominic De Groote (UGent) , Hanne Verschuere (UGent) , Marc Stemmler, Thomas Brabletz, Peter Vandenabeele (UGent) , Andreu Casali, Kyra Campbell, Steven Goossens (UGent) and Geert Berx (UGent)
- Organization
- Project
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- Mechanisms of ferroptosis mediated immunoregulation
- Targeting the Tumor Microenvironment in Colorectal Peritoneal Metastases
- Preclinical validation of novel anti-EMT therapy for malignant triple negative breast cancer
- Defining the role of ZEB1 in tumour initiation and progression of basal-like breast cancer
- Dissecting stromal-cancer cell interactions at the perivascular niche to detect and intercept the early metastatic process.
- MOlecular mechanisms of cellular DEath and Life decisions in Inflammation, Degeneration and Infection
- Cell Death Regulation and Role in Infection and Inflammatory Diseases
- Cell death activity regulation in inflammation and cancer
- Autophagy in inflammation and inflammatory disorders (ATLANTIS), from basic insights to experimental therapy
- Improving cancer therapy by modulating cell death and the microbiome in the gut
- Abstract
- Epithelial to Mesenchymal transitions (EMT) drive cell plasticity and are associated with cell features such as invasiveness, migration and stemness. They are orchestrated by select families of EMT-associated transcription factors, which exhibit pleiotropic roles in the malignant progression of various cancer types, such as breast and colorectal cancer (CRC). This has spurred interest in EMT as a promising target for the development of novel therapeutic strategies. In this study, we developed a phenotypic dual EMT Sensor screening assay, amendable to efficient high-throughput identification of small molecules interfering with EMT. In a proof-of-concept screening we identified anti-EMT repurposing drugs. From these, we validated RepSox, a selective inhibitor of the TGF-beta type I receptor ALK5, and demonstrated that it is potently blocking EMT in both breast and colorectal cancer cell lines in vitro. In addition, utilizing a Drosophila melanogaster metastatic CRC model we confirmed the ability of the identified anti-EMT hits to suppress metastatic behavior in vivo.
- Keywords
- HUMAN ENDOTHELIAL-CELLS, MESENCHYMAL TRANSITION, SELECTIVE-INHIBITION, DRUG-RESISTANCE, CANCER, EXPRESSION, ZEB1, METASTASIS, INDUCTION, DISCOVERY
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01JWZPMAZE4M8CAD6EZ1WQKNTJ
- MLA
- Jonckheere, Sven, et al. “Development and Validation of a High-Throughput Screening Pipeline of Compound Libraries to Target EMT.” CELL DEATH AND DIFFERENTIATION, vol. 32, no. 11, 2025, pp. 2078–92, doi:10.1038/s41418-025-01515-6.
- APA
- Jonckheere, S., Taminau, J., Adams, J., Haerinck, J., De Coninck, J., Verstappe, J., … Berx, G. (2025). Development and validation of a high-throughput screening pipeline of compound libraries to target EMT. CELL DEATH AND DIFFERENTIATION, 32(11), 2078–2092. https://doi.org/10.1038/s41418-025-01515-6
- Chicago author-date
- Jonckheere, Sven, Joachim Taminau, Jamie Adams, Jef Haerinck, Jordy De Coninck, Jeroen Verstappe, Kato De Clercq, et al. 2025. “Development and Validation of a High-Throughput Screening Pipeline of Compound Libraries to Target EMT.” CELL DEATH AND DIFFERENTIATION 32 (11): 2078–92. https://doi.org/10.1038/s41418-025-01515-6.
- Chicago author-date (all authors)
- Jonckheere, Sven, Joachim Taminau, Jamie Adams, Jef Haerinck, Jordy De Coninck, Jeroen Verstappe, Kato De Clercq, Evelien Peeters, Alexander Gheldof, Eva De Smedt, Vera Goossens, Dominique Audenaert, Aurelie Candi, Matthias Versele, Dominic De Groote, Hanne Verschuere, Marc Stemmler, Thomas Brabletz, Peter Vandenabeele, Andreu Casali, Kyra Campbell, Steven Goossens, and Geert Berx. 2025. “Development and Validation of a High-Throughput Screening Pipeline of Compound Libraries to Target EMT.” CELL DEATH AND DIFFERENTIATION 32 (11): 2078–2092. doi:10.1038/s41418-025-01515-6.
- Vancouver
- 1.Jonckheere S, Taminau J, Adams J, Haerinck J, De Coninck J, Verstappe J, et al. Development and validation of a high-throughput screening pipeline of compound libraries to target EMT. CELL DEATH AND DIFFERENTIATION. 2025;32(11):2078–92.
- IEEE
- [1]S. Jonckheere et al., “Development and validation of a high-throughput screening pipeline of compound libraries to target EMT,” CELL DEATH AND DIFFERENTIATION, vol. 32, no. 11, pp. 2078–2092, 2025.
@article{01JWZPMAZE4M8CAD6EZ1WQKNTJ,
abstract = {{Epithelial to Mesenchymal transitions (EMT) drive cell plasticity and are associated with cell features such as invasiveness, migration and stemness. They are orchestrated by select families of EMT-associated transcription factors, which exhibit pleiotropic roles in the malignant progression of various cancer types, such as breast and colorectal cancer (CRC). This has spurred interest in EMT as a promising target for the development of novel therapeutic strategies. In this study, we developed a phenotypic dual EMT Sensor screening assay, amendable to efficient high-throughput identification of small molecules interfering with EMT. In a proof-of-concept screening we identified anti-EMT repurposing drugs. From these, we validated RepSox, a selective inhibitor of the TGF-beta type I receptor ALK5, and demonstrated that it is potently blocking EMT in both breast and colorectal cancer cell lines in vitro. In addition, utilizing a Drosophila melanogaster metastatic CRC model we confirmed the ability of the identified anti-EMT hits to suppress metastatic behavior in vivo.}},
author = {{Jonckheere, Sven and Taminau, Joachim and Adams, Jamie and Haerinck, Jef and De Coninck, Jordy and Verstappe, Jeroen and De Clercq, Kato and Peeters, Evelien and Gheldof, Alexander and De Smedt, Eva and Goossens, Vera and Audenaert, Dominique and Candi, Aurelie and Versele, Matthias and De Groote, Dominic and Verschuere, Hanne and Stemmler, Marc and Brabletz, Thomas and Vandenabeele, Peter and Casali, Andreu and Campbell, Kyra and Goossens, Steven and Berx, Geert}},
issn = {{1350-9047}},
journal = {{CELL DEATH AND DIFFERENTIATION}},
keywords = {{HUMAN ENDOTHELIAL-CELLS,MESENCHYMAL TRANSITION,SELECTIVE-INHIBITION,DRUG-RESISTANCE,CANCER,EXPRESSION,ZEB1,METASTASIS,INDUCTION,DISCOVERY}},
language = {{eng}},
number = {{11}},
pages = {{2078--2092}},
title = {{Development and validation of a high-throughput screening pipeline of compound libraries to target EMT}},
url = {{http://doi.org/10.1038/s41418-025-01515-6}},
volume = {{32}},
year = {{2025}},
}
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