Scientists have identified GATA6 as a molecular switch that, when lost, causes colon cancer cells to transform into highly adaptable fetal-like cells. This transformation allows the cells to spread through the bloodstream and form new tumors in the liver. The study found that epigenetic changes, rather than genetic mutations, drive this metastatic process. Understanding this mechanism could lead to new strategies for preventing colorectal cancer from becoming deadly.

Scientists have identified a molecular switch that could help explain why colorectal cancer becomes more deadly. Researchers found that when levels of a gene-regulating factor known as GATA6 decline, cancer cells lose their normal identity and transform into highly adaptable, fetal-like cells that can spread through the bloodstream and form new tumours in the liver.

"We discovered that GATA6 loss acts as a critical switch that can change cancer cells in the primary tumor from non-metastatic to pro-metastatic. - Dr. Norihiro Goto"

The study suggests this transition is driven primarily by changes in how genes are activated or suppressed, rather than by new genetic mutations.

Researchers at Weill Cornell Medicine and the Massachusetts Institute of Technology have identified a key factor that may help colorectal cancer spread to the liver. Their findings suggest that losing GATA6, a transcription factor that helps control which genes are turned on or off, can push cancer cells into a more primitive and adaptable state that makes metastasis possible.

Understanding how this transformation occurs could lead to new strategies for preventing one of the deadliest aspects of colorectal cancer.

GATA6 normally serves as a molecular "identity keeper" in the cells that line the intestine, helping them maintain their specialised functions. However, the study, published June 22 in Cell Stem Cell, found that GATA6 levels are much lower in liver metastases from both mice and people with colorectal cancer.

The researchers also found that reduced GATA6 expression is associated with poorer patient outcomes. Once colorectal cancer spreads beyond its original site, treatment becomes far more challenging, and metastasis remains the leading cause of death from the disease.

For years, scientists have searched for genetic mutations that might trigger liver metastasis, but no clear driver mutations have emerged. Instead, the new study points to a different mechanism.

"We discovered that GATA6 loss acts as a critical switch that can change cancer cells in the primary tumor from non-metastatic to pro-metastatic," said Dr. Norihiro Goto, assistant professor of medicine in the Division of Gastroenterology & Hepatology at Weill Cornell, who co-led the research.