There are more than 200 different cell types in the human body. Each cell is specialized to perform a specific function or form a specialized tissue. When cells don’t function properly, different diseases can occur. Scientists have now conducted research that opens up a whole new world inside our cells.
Every minute of every day, our bodies adapt to meet the needs of the moment. When we eat carbohydrates, exercise, or get sick, chemical reactions in our cells kick in, slow down, or change strategy to give us the energy and strength we need. All of this is happening without us knowing it, which perhaps explains why so little is known about how the body perceives and responds to these constant demands. In search of answers to this question, scientists at the University of Utah Health conducted new research. Their study, published in Science, uncovers a vast network of interactions that suggest how cells adapt in real time to withstand stresses on our health.
Deeper Understanding of How Our Cells Work
These discoveries—and the technology that made them possible—have become the foundation for biotechnology company Atavistik Bio, co-founded by Jared Rutter, Ph.D., distinguished professor in the Department of Biochemistry at the University of Utah. The company uses this new understanding to accelerate drug discovery for metabolic diseases and cancer. At a more fundamental level, progress deepens our knowledge of how cells and our bodies work.
The network described in the study represents an underestimated level of regulation in cells that comes from an unexpected source. For almost 20 years, Rutter’s lab has been studying metabolism, the chemical reactions that generate energy and form essential components that keep cells functioning properly. Their new research shows that intermediates in these chemical reactions are more than passive building blocks and fuel sources for cells, as has long been assumed.
Instead, these intermediates, along with other metabolites, form an expansive web of sentinels that monitor the environment and prompt cells to adapt when necessary. They do this by interacting with proteins and changing how they work. Does a Large Meal Pump Too Many Carbs Into Your Body? Or too much fat? Like a railroad switch directing a train onto a new track, these protein-metabolite interactions shift metabolic processes to break down these nutrients and stabilize the course.
Development of New Therapeutic Approaches
The study’s first author, Kevin Hicks, Ph.D., developed a new technology called MIDAS that reveals the size of the regulatory network that acts at the interface between environmental stimuli and cellular metabolism, dubbed the protein-metabolite interactome. The highly sensitive technique identified interactions that had never been observed before. An analysis of 33 human proteins involved in the conversion of carbohydrates into fuel revealed 830 interactions with metabolites. Given that there are thousands of proteins in the cell, the overall size of the network is expected to be much larger. Metabolic processes that get out of hand can lead to diseases and many ailments. The researchers believe that shedding light on additional interactions in the network will lead to a better understanding of the root causes of disease and the development of new therapeutic approaches to get things back on track.
Breast Cancer Cells in the Lungs Can Trigger Secondary Tumors
The importance of our cells functioning properly is demonstrated when diseases such as cancer develop. Recent research has discovered why breast cancer cells that have spread to the lungs can “wake up” after years of sleep and form incurable secondary tumors. Her research uncovers the mechanism that sets off this breast cancer “time bomb” — and suggests a strategy to defuse it.
Patients with estrogen receptor-positive (ER+) breast cancer — the most common type — have an ongoing risk of their cancer recurring in another part of their body many years or even decades after it was originally diagnosed and treated. When breast cancer cells spread from the first cancer in the breast to other parts of the body, it is called secondary or metastatic breast cancer, which can be treated but not cured. The new study, published in the journal Nature Cancer, showed how molecular changes in the lungs that occur during aging can help these secondary tumors to grow.
Cancer Growth Blockers Called Imatinib
The team from the Institute of Cancer Research, London, found that the PDGF-C protein present in the lungs plays a key role in whether inactive breast cancer cells sleep or “wake up”. They discovered that an increase in PDGF-C levels, which is more likely with aging lungs or when their tissue becomes damaged or scarred, can cause the dormant cancer cells to grow and develop into secondary breast cancer. The researchers then looked at whether blocking PDGF-C activity could help to prevent these cells from “waking up” and preventing secondary tumors from growing.
Researchers at the Breast Cancer Now Toby Robins Research Center at the Institute of Cancer Research worked in mice with ER+ tumors and targeted PDGF-C signaling with an existing cancer growth blocker called imatinib, which is currently used to treat patients with chronic myeloid leukemia . The mice were treated with the drug both before and after the tumors developed. Cancer growth in the lungs was significantly reduced in both groups.
The researchers now plan to better understand how patients might benefit from the existing drug imatinib, and in the long term aim to develop more specific treatments that target the ‘reawakening’ mechanism.”