US researchers have identified a protein that helps the gut repair itself after injury but that colorectal cancer cells also use to spread to other organs in mice. 

Colorectal cancer is one of the most common cancers and can become much harder to treat when cancer cells spread from the gut to other organs, such as the liver or lungs.  

Researchers at Memorial Sloan Kettering Cancer Center, New York, found that after gut injury in mice, cells activate a temporary stress response and begin to exhibit stem-cell-like features to produce new gut cells and regenerate the tissue. Mice lacking the protein ZFP36L2, or ZFP, could not shut down the stress response, leaving cells stuck in an intermediate state and preventing proper gut regeneration. 

The team then reduced ZFP levels in 3D cell cultures grown from patients’ colorectal cancer cells that had spread to the liver. When implanted in mice, these cells failed to form tumours in distant organs, suggesting that cancer cells depend on ZFP to return to a stem cell state and spread. However, patient tumours without ZFP at all were also more likely to develop some resistance to cancer treatment. 

“The cancer cells can’t enter the stem cell state to make new colon cancer cells. So they get stuck in this stress-response state — which pushes the cancer cells to rapidly adapt. Under this pressure, cells that can switch identities and survive get selected for, making these cancers much harder to treat,” said Karuna Ganesh, from the Memorial Sloan Kettering Cancer Center and senior author of the study published in Nature. 

Dr. Karuna Ganesh. CREDIT: Memorial Sloan Kettering Cancer Center