Research in protein breakdown opens doors for cancer treatment

A team of researchers, led by McGill Professor Dr. Barry Posner,  has recently uncovered the importance of growth factors in maintaining healthy cells. Growth factors are molecules that stimulate and regulate cellular growth.

Put simply, our cells are involved in a continuous cycle of breaking down and re-growth, much like the process of building structures with Legos. Once all the Lego pieces are used up, old structures must be broken down and the pieces reused to build new ones. Since there are a limited number of Lego pieces, it is impossible to continue to build structures without breaking down the old ones and using them for their parts.

Cells, too, must be broken down in order for new cell growth to occur, and growth factors facilitate the process.

Insulin, a hormone that stimulates glucose uptake, is also a growth factor. Prior to the discovery of insulin, children with Type I diabetes were characterized by a gaunt appearance. When provided with insulin, a dramatic physical transformation from diminutive to healthy occurred in these children over several weeks.

Dr. Posner’s lab is primarily interested in insulin and growth factors, and their relationship to disease. Recently, they have been focusing on the role inhibiting acidification plays in the growth response by studying certain cellular structures.

The master molecule that is responsible for growth is called mTOR, (Mammalian Target of Rapamycin). When stimulated, this molecule will not act unless it has a large enough supply of amino acids to use to build new molecules.

The relationship between acidification and the growth factor can also be likened to building a house. Even with plans, a construction worker cannot build a structure without a continuous supply of bricks. If this supply is cut off, the construction worker will stop building until more bricks are provided.

Likewise, when growth factors stimulate the acidification of lysosomes (organelles that contain enzymes that degrade cells), the enzymes within lysosomes have the optimal pH condition to break down proteins within cells in order to provide the mTOR molecule with essential building blocks, amino acids. Without sufficient supplies, this molecule will not support the synthesis of new proteins.

Understanding the role of acidification and the growth response opens new avenues for cancer treatment.

“What we know is this: everyone is trying to find ways of blocking growth factors in cancer cells, because it looks like, in a number of cancers, growth factor stimulation is an important facet of the … proliferative process that characterizes the growth and spread of cancer cells,” Dr. Posner said.

For instance, Type II diabetes carriers show an increase in an incidence of cancer. They also have insulin resistance, or higher-than-normal insulin levels in certain tissues. Cancer cells appear to respond to this increase in availability of insulin to their advantage. As insulin is a growth factor, cancer cells use it to promote cell division and rapidly proliferate. Essentially, it appears that insulin resistance promotes the growth of cancer cells.

“There is now another target that we can look at for regulation of growth factor action [the acidification of vacuolar areas]. If we can find ways of probing that target with new molecules, we might be able to inhibit their growth promoting effects and contribute to the control of cancer cells,” Dr. Posner said.

Insulin is necessary for the body. However, if the growth promoting action of insulin on cancer cells is blocked, the increased incidence of cancer in Type II diabetes will likely decline.

This finding is one of many that are contributing to the development of cancer drugs and new treatments.

“I think it will stimulate the imagination… I hope it will promote my colleagues to think more about the regulation of the growth process.”

Leave a Comment

Your email address will not be published. Required fields are marked *