When Andrea Pérez González deleted two tiny molecular "gatekeepers" from cancer cells in mice, something remarkable happened: the tumors stopped spreading.
Pérez González, a researcher at the Université Libre de Bruxelles in Belgium, was studying how cancer cells break free from their original tumor and travel through the bloodstream to infect other organs — a process called metastasis. It's this spread that kills about 90 percent of all cancer patients, even when the original tumor is caught early.
Working with colleague Gabriel Windels and led by Professor Cédric Blanpain, Pérez González identified two transcription factors — named Klf5 and Pitx1 — that act like gatekeepers controlling whether cancer cells can make the transition from stationary to mobile. Think of them as tiny switches that, when turned on, allow cancer cells to escape their neighbors and float away to start new tumors elsewhere.
"Uncovering that the suppression of Pitx1 or Klf5 drastically reduced metastasis in mouse models was fascinating," Pérez González said, "suggesting that these new regulators controlling EMT states could represent potential therapeutic targets to prevent metastasis."
The team used advanced single-cell sequencing techniques to watch individual cancer cells as they changed. They found that Klf5 and Pitx1 control the early stages of this transition — the point at which cancer cells first learn to detach and spread. A second pair of factors, Nfatc1 and Creb3l1, handle the later stages of the process.
When the researchers genetically removed Klf5 and Pitx1 from mouse tumors, metastasis dropped dramatically. The finding is significant because the same cellular machinery exists in human cancers too. The team confirmed that the regulatory networks they discovered in mice closely match what's seen in human tumor data.
Blanpain said the discovery points to a fundamentally new approach. Instead of trying to kill cancer cells after they've spread — which is extremely difficult — doctors might one day keep cancer cells "locked in nonmetastatic states, preventing metastatic dissemination."
Of course, this research was done in mice, not people. Clinical treatments are still far away. But clinical strategies to prevent metastasis remain "a major unmet clinical need," Blanpain acknowledged. Every year, millions of lives are cut short because cancer spreads before doctors can catch it. Research like this offers a new roadmap for keeping cancer locked in place.
The study was published in the journal Nature Communications in 2026.