A chemical chain reaction that controls organ size in animals ranging from insects to humans could mean the difference between normal growth and cancer.
The Johns Hopkins study, published in today?s issue of Cell, describes how organs can grow uncontrollably huge and become cancerous when this chain reaction is stimulated.
“This chain reaction, a domino-like chain of events we call the Hippo pathway, adds a single chemical group on a protein nicknamed Yap,” lead author Duojia Pan, said. “The good news is that maybe all organ growth can be reduced to this one chemical event on the Yap protein ? but the better news is that we potentially have a new target for cancer therapy.”
The Yap protein, when found in the cell?s nucleus, stimulates cell growth and division, he said. “We already know that in many cancer cells, they have an inordinate amount of this protein.”
However, when a phosphate is added to Yap, the protein leaves the nucleus and cell division stops.
Previous research has shown that excess quantities of Yap in fruit flies supercharges growth-inducing genes and causes organs to overgrow.
In Pan?s study, the research team genetically altered mice to make high levels of Yap protein, but only in their liver cells. These animals? livers grew to five times normal size, and often were dotted with large tumors.
“A drug that somehow turns off Yap might also stop cancer cells from growing,” says Pan, “and manipulating the Hippo pathway could provide a way to grow organs to a predetermined size for transplantation.”
In healthy people, Yap is prevalent in young and growing children, and the body regulates its presence as a way of controlling organ growth, Pan said. “In adults, it might be present in certain cells, maybe in stem cells that are always dividing and creating blood cells, brain cells and other tissues.”
