Researchers at Weill Cornell Medicine and MIT discovered a key reason why colon cancer can move to the liver. When a protein named GATA6 disappears, cancer cells become more primitive and can spread more easily.
GATA6 works like an identity badge for cells that line the intestine. It tells them which genes to turn on or off. In liver metastases taken from mice and people, the amount of GATA6 was much lower. Patients with low GATA6 tended to do worse.
For a long time, scientists looked for DNA mutations that cause liver spread, but none stood out. This study points to a different cause – changes in how genes are read, not the gene sequence itself.
Mini‑Tumors Show the Early Steps
Looking only at cancer that has already reached the liver misses the early changes. To see those, the team grew tiny 3‑D clusters called organoids from liver tumors. They placed the organoids into mouse colons. The tumors grew, became more aggressive, and later spread to the liver.
Each round let the scientists watch how the cells changed. They found that losing GATA6 gave the cells “lineage plasticity”—the ability to change their identity. Without GATA6, the cells turned on new gene programs and looked more like early‑development (fetal) cells. This made them better at moving through blood and forming new tumors.
A Shift From LGR5‑Positive to LGR5‑Negative Cells
One sign of this change was the loss of a marker called LGR5, which is common in normal intestinal stem cells. Earlier work showed that cells without LGR5 can start liver metastases. The new research proved that turning off GATA6 pushes cells from an LGR5‑positive state to an LGR5‑negative, fetal‑like state that can spread.
When the researchers added GATA6 back, or activated related pathways, the cancer cells were less likely to travel to the liver.
What This Means for Patients
Low GATA6 could become a warning sign. Tumors with little GATA6 might contain more cells ready to switch into a spreading mode. Doctors could use this information to watch those patients more closely or treat them more aggressively.
The study also hints at new treatments. If scientists can keep cancer cells locked in their original identity, they might stop the cells from becoming flexible enough to metastasize. However, any therapy must avoid hurting normal tissue‑repair processes that use the same pathways.
Future work will search for weaknesses that appear only in GATA6‑deficient cells and will explore how the surrounding liver environment helps the switch happen.
"We need ways to stop the spread of cancer before it even starts," said Dr. Goto. "Our findings bring us a step closer to that goal."