Researchers have identified how reduced levels of the GATA6 factor enable colorectal cancer cells to adopt a fetal-like state and metastasize to the liver. The findings point to epigenetic changes rather than genetic mutations as a key driver of this deadly progression.
Scientists at Weill Cornell Medicine and the Massachusetts Institute of Technology found that loss of GATA6 allows cancer cells to shed their specialized identity. This shift promotes lineage plasticity and helps cells travel through the bloodstream to form new tumors.
The study, published June 22 in Cell Stem Cell, used organoid models implanted in mice to track the early stages of metastasis. Dr. Norihiro Goto, who co-led the research, said GATA6 loss acts as a critical switch that turns non-metastatic cells into pro-metastatic ones.
Lower GATA6 expression was observed in both mouse and human liver metastases and correlated with poorer outcomes. Restoring GATA6 activity reduced the cells' ability to spread.
The results suggest GATA6 could serve as a biomarker for metastatic risk and point to potential strategies for blocking early spread without disrupting normal tissue repair.
