March 13, 2013 — A new study by Harvard School of Public Health (HSPH) researchers is the first to identify the primary mechanism controlling a metabolic process essential for cell growth and proliferation. This pathway is centered around the mTOR protein, which relays growth signals to cells in response to external stimuli, including insulin and nutrients. The scientists speculate that one day researchers may be able to use this new knowledge to develop treatments for certain cancers which have uncontrolled mTOR signaling.
The study appeared in the March 15, 2013 issue of Science.
Cells closely monitor the availability of growth factors, nutrients, and energy. They respond to growth signals by generating nucleotides, the building blocks of RNA and DNA, which are essential to replicating the cellular genetic material for the new cells.This study is the first to demonstrate a novel control mechanism through which this process occurs, providing a molecular link between growth signals and the synthesis of new nucleotides.
The mTOR protein is expressed in all cells in the human body. Its signaling pathway senses and integrates cellular growth signals and acts as a conduit between these signals and the control of specific energy- and nutrient-consuming biosynthetic processes, such as protein and lipid synthesis. This study extends these processes essential to cell growth to include nucleotide synthesis. These processes can be activated to heal a wound or expand immune cell populations to fight off pathogens. But they can also be activated by genetic and environmental factors that underlie common human diseases. mTOR signaling is activated in up to 80% of human cancers and is elevated under conditions of obesity and type 2 diabetes.
This study’s findings suggest that uncontrolled mTOR signaling present in most cancer cells is likely to contribute to the uncontrolled growth of these cells, at least in part, by facilitating the increased demand for RNA and DNA in these cells.
“This is a novel discovery regarding the fundamental control of cellular metabolism,” said senior author Brendan Manning, associate professor of genetics and complex diseases at HSPH. “We hope to take advantage of this new knowledge to develop therapeutic strategies to treat cancer and tumor syndromes which have uncontrolled mTOR signaling.”
Other HSPH authors include Issam Ben-Sahra and Jessica Howell, who are both postdoctoral research fellows in the Department of Genetics and Complex Diseases.
Illustration by Jessica Howell