GATA6 loss drives colorectal cancer metastasis

Researchers at Weill Cornell Medicine and the Massachusetts Institute of Technology have identified that loss of the transcription factor GATA6 acts as a molecular switch enabling colorectal cancer cells to undergo lineage plasticity, reverting to a fetal-like state that promotes liver metastasis. The study, published June 22 in Cell Stem Cell, shows that GATA6 loss triggers epigenetic changes rather than genetic mutations, increasing metastatic burden in mouse models without affecting primary tumor growth. GATA6 levels are lower in liver metastases from patients and correlate with poorer outcomes. The findings suggest GATA6 could serve as a biomarker for metastatic risk and point to potential therapeutic strategies aimed at maintaining cellular identity. The research was supported by multiple foundations and the United States — National Institutes of Health.