As bodily organs go, the liver pales in comparison to the powerful heart or the conscious brain. It does have one remarkable ability that sets it apart from the rest, though: It can grow back, even if more than a half of it is removed.
That can be important to survival, but Wendong Huang, Ph.D., assistant professor of gene regulation and drug discovery at City of Hope, believes this trait also might lie at the core of liver cancer.
The liver, which rests just under the diaphragm and next to the stomach, plays a major role in breaking down toxins and metabolizing many nutrients. It produces bile acids, which help the body absorb fatty acids and some vitamins in the small intestine.
Wendong Huang studies the connection between liver regrowth and cancer. (Photo by Markie Ramirez)
If the liver is damaged, even severely, it can heal itself completely. Even with as little as 30 percent of its original mass remaining, the liver can regrow to full size. And no one knows how.
Huang is studying how the liver repairs itself and how that ability is linked to liver cancer. He believes one of the key players could be a protein called farnesoid X receptor, or FXR.
FXR belongs to a class of proteins called nuclear hormone receptors. These proteins interact with hormones and act as switches to turn genes on and off.
FXR controls genes that regulate the amount of bile acids produced by the liver. Too much bile acid can be toxic, so if bile acid levels are high, FXR kicks in, turning on the machinery that lowers them.
In previous research, Huang found that FXR also is involved with liver repair following injury. Livers that were unable to make the FXR protein could not control their bile acid levels and had difficulty regrowing. Huang believes bile acid regulation and liver regrowth are directly connected.
“The main function for FXR is to control bile acid levels,” he said. “If they get too high, FXR turns on genes that metabolize them,” lowering their levels. But if the liver is injured and does not have enough of the FXR-controlled machinery it needs to bring bile acid levels into balance, FXR takes a second step: It stimulates the liver to regrow in an effort to beef up the entire organ, giving it enough power to finish the job.
Huang also found a connection between FXR and liver cancer. Those same mice lacking FXR always developed liver tumors after about a year.
“If the cycle of tissue damage and repair gets out of control or repeats too often, it can lead to permanent damage and even cancer,” he said.
Now Huang wants to delve deeper into this mystery to understand exactly how FXR stimulates liver regrowth and how that is connected to cancer in humans.
Huang believes the research could find much-needed answers. “This could help not just liver cancer patients, but patients with other cancers, as well,” he said. “If we can understand this, it could help a lot of people.”