By analyzing individual cancer cells, researchers at the Free University of Bruxelles (ULB) discovered the transcriptional regulators that govern tumor EMT, identified key master regulators that control metastasis, and uncovered new therapeutic vulnerabilities to halt metastatic dissemination.
Metastasis is the process by which cancer cells spread to other organs far from their original site and is responsible for 90% of deaths in cancer patients. To cause metastasis, cancer cells undergo epithelial-to-mesenchymal transition (EMT). This is a cellular process that allows cancer cells to detach from neighboring cells, spread into the blood, and reach distant organs. Rather than a simple on/off switch, EMT progresses through a variety of intermediate “hybrid” states. These hybrid states have the highest potential for metastasis. However, the specific transcriptional regulators governing different EMT states and metastases remained poorly understood.
In one study, a research team led by Cédric Blancpain, MD/PhD, a researcher at the WEL Institute, director of the Stem Cell and Cancer Research Institute, and professor at the Vrije Universiteit Bruxelles, discovered the precise transcription factors that determine EMT transition and control metastasis.
Andrea Pérez González, Gabriel Windels and colleagues used a multidisciplinary approach that combines advanced sequencing techniques and functional experiments at single-cell resolution to identify transcription factors. Klf5 and Pit x1 Serves as a gatekeeper and key regulator of the early ED transition. genetic deletion of Klf5 and Pit x1 Metastasis formation was dramatically reduced. On the contrary, they found that: Nfatc1 and Kleb 3l1 Regulate late paramedic states.
reveal the oppression of Pit x1 or Klf5 It is interesting that metastasis was dramatically reduced in the mouse model, suggesting that these new regulators of the EMT state may represent new potential therapeutic targets to prevent metastasis. ”
Dr. Andrea Pérez González, first author of the paper
Because the regulatory networks discovered in mouse tumors closely match human data, these findings reveal fundamental therapeutic vulnerabilities to prevent metastasis. “Clinical strategies to prevent or block metastases remain a major unmet clinical need. We hope that blocking the factors involved in metastasis formation will: Pit x1 and Klf5This would allow us to keep cancer cells in a non-metastatic state and prevent them from spreading,” commented Professor Cédric Blancpain, who led the study.
sauce:
Free University of Brussels
Reference magazines:
Perez-González, A.et al. (2026). Single-cell multiomics elucidates the transcriptional networks that control different EMT tumor states. nature communications. DOI: 10.1038/s41467-026-75521-8. https://www.nature.com/articles/s41467-026-75521-8
