September 21 : Johns Hopkins researchers have described how the body organs can grow uncontrollably huge and become cancerous, when a chemical chain reaction that controls the growth of organs in living beings ranging from insects to humans is perturbed.

“This chain reaction, a domino-like chain of events we call the Hippo pathway, adds a single chemical group on a protein nicknamed Yap. 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,” says lead author Dr. Duojia Pan, associate professor of molecular biology and genetics.

A study of fruit flies had recently shown that too much of Yap supercharges growth-inducing genes, and causes organs to overgrow. The new study involved mice so as to determine whether the same effect occurred in mammals too.

During the course of study, the researchers genetically altered mice to make high levels of Yap protein, but only in liver cells. These animals’ livers grew to be five times the size of a normal mouse liver and often were dotted with large tumours.

“We were totally amazed. Five times is just a huge effect,” says Pan.

Upon looking at a variety of human cancer cells, the researchers found that 20 to 30 per cent of them contained increased levels of Yap.

“We think it might be the extra Yap in these cells contributing to their cancerous growth,” says Pan.

Just like most proteins, Yap exists in more than one form. In the present case, the protein existed in two forms, one with and one without a chemical phosphate tag attached.

According to the researchers, such tags can dramatically alter what proteins do in the body.

When the cells are engineered to stop or slow growth, Yap in them has its phosphate attached and moves from the nucleus—the brain centre of the cell—into the main body of cells, or cytoplasm.

“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 pre-determined size for transplantation.” (ANI)